High temperature melting

ABSTRACT

The present invention relates to methods for making wear and oxidation resistant polymeric materials by high temperature melting. The invention also provides methods of making medical implants containing cross-linked antioxidant-containing tough and ductile polymers and materials used therewith also are provided.

This application claims priority to U.S. Application Ser. No.61/154,134, filed Feb. 20, 2009; the entirety of which is herebyincorporated by reference.

FIELD OF THE INVENTION

The present invention relates to methods for making wear resistantpolymeric materials. Methods of making medical implants containingantioxidant-containing wear resistant polymers and materials usedtherewith also are provided. Wear resistant polymeric materials andmedical implants containing such materials are also provided.

BACKGROUND OF THE INVENTION

It is advantageous to have tough and ductile polymeric materials, forexample, Ultrahigh Molecular Weight Polyethylene (UHMWPE), for totaljoint implants without sacrificing oxidative stability and wearresistance. Wear resistance can be improved by cross-linking. However,crosslinking reduces the toughness and ductility of the material.Therefore, it is desirable to have a method to increase toughness andductility of wear and oxidation resistant polymeric material.

Various methods of making cross-linked polymeric materials are known inthe field. Saum et al. (U.S. Pat. No. 6,316,158) described melting andsubsequent radiation crosslinking of UHMWPE to increase ductilitysubstantially through an increase in elongation at break. However, Saumet al. suggested not to using antioxidants in this process. The UHMWPEpreform material used by Saum et al. does not contain antioxidants, asthey believed that the presence of antioxidant may cause adverse effectsin medical applications.

This application describes methods and approaches not found in the fieldfor making cross-linked, wear and oxidation resistant, tough and ductilepolymers, and materials used therein.

SUMMARY OF THE INVENTION

The present invention relates generally to methods for makingcross-linked, wear and oxidation resistant polymeric materials. Methodsof making medical implants containing cross-linked andantioxidant-containing polymers, and materials obtainable thereby, andmaterials used therewith, also are provided. More specifically, theinvention relates to methods of making cross-linked, wear and oxidationresistant, tough and ductile polymeric materials by high temperaturemelting. Also, the invention relates to methods of making crosslinked,wear and oxidation resistant polymeric materials with a gradient ofantioxidants and/or a gradient in crosslink density.

In one embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) irradiating astarting material by ionizing radiation, wherein the starting materialis a polymeric material or a mixture of polymeric materials, wherein thepolymeric material is blended or doped with at least one antioxidant oralready has a gradient of antioxidant(s); ii) heating the irradiatedstarting material to a temperature of about 200° C. or more; iii)continue heating the irradiated material following irradiation; and iv)cooling the heated polymeric material, thereby forming a wear resistantpolymeric material.

In one embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) irradiating astarting material by ionizing radiation, wherein the starting materialis a polymeric material or a mixture of polymeric materials, wherein thepolymeric material is blended or doped with at least one antioxidant oralready has a gradient of antioxidant(s); ii) heating the irradiatedstarting material to a temperature of about 120° C. or more; iii)continue heating the irradiated material following irradiation; and iv)cooling the heated polymeric material, thereby forming a wear resistantpolymeric material.

In another embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) irradiating astarting material by ionizing radiation, wherein the starting materialis a polymeric material or a mixture of polymeric materials, wherein thepolymeric material is blended or doped with at least one antioxidant oralready has a gradient of antioxidant; ii) heating the irradiatedstarting material to a temperature of about 200° C. or more; iii)continue heating the irradiated material following irradiation; iv)cooling the heated and irradiated polymeric material; and v) doping theirradiated polymeric material with at least one antioxidant, therebyforming a wear resistant polymeric material.

In another embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) heating astarting material to a temperature of about 200° C. or more, wherein thestarting material is a polymeric material or a mixture of polymericmaterials, wherein the polymeric material is blended or doped with atleast one antioxidant or already has a gradient of antioxidant; ii)continue heating the starting material; iii) irradiating the heatedstarting material by ionizing radiation; and iv) cooling the irradiatedmaterial, thereby forming a wear resistant polymeric material.

In another embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) heating astarting material to a temperature of about 200° C. or more, wherein thestarting material is a polymeric material or a mixture of polymericmaterials, wherein the polymeric material is blended or doped with atleast one antioxidant or already has a gradient of antioxidant; ii)continue heating the starting material; iii) cooling the heatedmaterial; iv) irradiating the material by ionizing radiation; v) heatingthe irradiated material to a temperature above or below the meltingpoint of the polymeric material; and vi) cooling the heated andirradiated material from v), thereby forming a wear resistant polymericmaterial.

In another embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) heating astarting material to a temperature of about 200° C. or more, wherein thestarting material is a polymeric material or a mixture of polymericmaterials, wherein the polymeric material is blended or doped with atleast one antioxidant or already has a gradient of antioxidant; ii)continue heating the starting material; iii) cooling the heatedmaterial; iv) irradiating the material by ionizing radiation; and v)doping the irradiated polymeric material with at least one antioxidant,thereby forming a wear resistant polymeric material.

In another embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) heating astarting Material to a temperature of about 200° C. or more, wherein thestarting material is a polymeric material or a mixture of polymericmaterials, wherein the polymeric material is blended or doped with atleast one antioxidant or already has a gradient of antioxidant; ii)continue heating the starting material; iii) cooling the heatedmaterial; iv) irradiating the material by ionizing radiation; v) dopingthe irradiated polymeric material with at least one antioxidant; vi)heating the antioxidant-doped and irradiated material to a temperatureabove or below the melting point of the polymeric material; and vii)cooling the heated and irradiated material from vi), thereby forming awear resistant polymeric material.

In another embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) irradiating astarting material by ionizing radiation, wherein the starting materialis a polymeric material or a mixture of polymeric materials, wherein thepolymeric material is blended or doped with at least one antioxidant orhaving a already has of antioxidant; ii) heating the irradiated startingmaterial to a temperature of about 200° C. or more; iii) continueheating the irradiated material following irradiation; iv) cooling theheated polymeric material; v) irradiating the material by ionizingradiation; and vi) doping the irradiated polymeric material with atleast one antioxidant, thereby forming a wear resistant polymericmaterial.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the starting material is obtainedby a method comprising the steps of: i) blending one or more polymeric,materials; ii) heating the polymeric blend to a temperature of about200° C. or more; and iii) cooling and consolidating the polymeric blend.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the starting material is obtainedby a method comprising the steps of: i) blending one or more polymericmaterials with at least one antioxidant; ii) heating theantioxidant-polymeric blend to a temperature of about 200° C. or more;and iii) cooling and consolidating the polymeric blend.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the wear resistant polymericmaterial is cross-linked.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the heating is continued for atleast for one minute, 10 minutes, 20 minutes, 30 minutes, one hour, twohours, five hours, ten hours, 24 hours, or more.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the starting material is heated toa temperature between about 200° C. and about 500° C. or more.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the starting irradiated materialis heated to a temperature between about 200° C. and about 500° C. ormore.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the starting material is heated toa temperature of about 200° C., about 220° C., about 250° C., about 280°C., about 300° C., about 320° C., about 350° C., about 380° C., about400° C., about 420° C., about 450° C., about 480° C. and about 500° C.or more.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the starting material is heated toa temperature of about 300° C. for about five hours.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the heating is carried out in aninert environment.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the polymeric material is UHMWPEresin, powder, or flake.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the polymeric material iscompression molded to a second surface prior to high temperaturemelting, thereby making an interlocked hybrid material, and wherein thesecond surface is a porous metal.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the doping is carried out bysoaking the polymeric material or medical implant in the antioxidant forabout 0.1 hours to about 72 hours, for example, the antioxidant isvitamin E.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the polymeric is selected from agroup consisting of a low-density polyethylene, high-densitypolyethylene, linear low-density polyethylene, ultra-high molecularweight polyethylene (UHMWPE), or a mixture thereof.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the irradiation is carried out inan atmosphere containing between about 1% and about 22% oxygen.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the irradiation is carried out inan inert atmosphere, and wherein the atmosphere contains gases selectedfrom the group consisting of nitrogen, argon, helium, neon, or the like,and a combination thereof.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the radiation dose is betweenabout 25 and about 1000 kGy, for example, preferably, the radiation doseis about 65 kGy, about 75 kGy, or about 100 kGy.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein reduction of free radicals in thecross-linked polymeric material is achieved by heating the polymericmaterial in contact with a non-oxidizing medium, wherein thenon-oxidizing medium is an inert gas, an inert fluid, or apolyunsaturated hydrocarbon selected from the group consisting ofacetylenic hydrocarbons such as acetylene; conjugated or unconjugatedolefinic hydrocarbons such as butadiene and (meth)acrylate monomers; andsulphur monochloride with chloro-tri-fluoroethylene (CTFE) or acetylene.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the polymeric material isirradiated at a temperature of about 40° C., about 75° C., about 100°C., about 110° C., about 120° C., about 130° C., about 135° C., about140° C., about 145° C., about 150° C., about 155° C., about 160° C.,about 165° C., about 170° C., about 175° C., about 180° C., about 185°C., about 190° C., or about 195° C.

In another embodiment, the invention provides medical devices comprisingthe polymeric material made according to any of methods disclosedherein.

In another embodiment, the invention provides medical devices comprisinga cross-linked polymeric material made according to any of methodsdisclosed herein.

In another embodiment, the invention provides medical devices comprisinga polymeric material with a gradient of crosslink density made accordingto any of methods disclosed herein.

In another embodiment, the invention provides medical devices comprisinga tough, and ductile polymeric material made according to any of methodsdisclosed herein.

In another embodiment, the invention provides medical devices comprisinga cross-linked, wear and oxidation resistant, tough, and ductilepolymeric material made according to any of methods disclosed herein.

According to one aspect of the invention, the medical device iscontacted, diffused, or homogenized with one or more antioxidants in asupercritical fluid, for example, CO₂.

According to one aspect of the invention, the medical device is selectedfrom the group consisting of acetabular liner, shoulder glenoid,patellar component, finger joint component, ankle joint component, elbowjoint component, wrist joint component, toe joint component, bipolar hipreplacements, tibial knee insert, tibial knee inserts with reinforcingmetallic and polymeric posts, intervertebral discs, interpositionaldevices for any joint, sutures, tendons, heart valves, stents, andvascular grafts.

According to another aspect of the invention, the medical device is anon-permanent medical device, wherein the non-permanent medical deviceis selected from the group consisting of a catheter, a balloon catheter,a tubing, an intravenous tubing, and a suture.

According to another aspect of the invention, the medical device ispackaged and sterilized by ionizing radiation or gas sterilization,thereby forming a sterile, highly cross-linked, oxidatively stablemedical device.

According to one aspect of the invention, the doping is carried out bysoaking the polymeric material or the medical implant in one or moreantioxidant(s) or their solutions, preferably, for about 5 minutes toabout 100 hours or more, more preferably, for about an hour, about 30minutes, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or about 16hours, and/or the antioxidant is heated to about 120° C. and the dopingis carried out at about 120° C., and/or the antioxidant is warmed toabout room temperature and the doping is carried out at room temperatureor at a temperature between room temperature and the peak meltingtemperature of the polymeric material or less than about 137° C., and/orthe cross-linked polymeric material is heated at a temperature below themelt of the cross-linked polymeric material. Depending upon thepolymeric material selected, heat treatment, homogenization and othertemperatures are determined in view of melting temperatures of theselected polymeric material.

According to another aspect of the invention, the doping is carried outby soaking the polymeric material or medical implant in the antioxidant,preferably, for about 5 minutes to about 100 hours or more, morepreferably, for about an hour, about 30 minutes, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, or about 16 hours, and/or the doping is carriedout at a temperature above the melting point of the polymeric material.For example, the doping is carried out at a temperature of about 140°C., about 145° C., about 150° C., about 155° C., about 160° C., about165° C., about 170° C., about 175° C., about 180° C., about 185° C.,about 190° C., about 195° C., about 200° C., about 250° C., about 280°C., about 300° C., about 320° C., about 350° C., about 380° C., about400° C., or more.

According to another aspect of the invention, the polymeric material isa polypropylene, a polyamide, a polyether ketone, or a mixture thereof;wherein the polyolefin is selected from a group consisting of alow-density polyethylene, high-density polyethylene, linear low-densitypolyethylene, ultra-high molecular weight polyethylene (UHMWPE), or amixture thereof; and wherein the polymeric material is polymeric resin,including powder, flakes, particles, or the like, or a mixture thereofor a consolidated resin.

In one embodiment, the antioxidant-doped or antioxidant-blendedpolymeric material is homogenized at a temperature below or above themelting point of the polymeric material for about an hour to severaldays.

In another embodiment of the invention, the oxidation-resistantcross-linked medical implant preform is further homogenized followingthe irradiation step by heating to a temperature below or above the meltto allow diffusion of one or more antioxidants.

In another embodiment of the invention, the antioxidant-doped polymericmaterial, the oxidation-resistant medical implant preform, or themedical implant preform is homogenized before and/or after irradiation,by thermally annealing at a temperature below or above the melting pointof the polymeric material.

In another embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) irradiating astarting material by ionizing radiation, wherein the starting materialis a mixture of polymeric materials, wherein the polymeric material hasa gradient of antioxidants containing Irganox® 1010-rich surface regionsand vitamin E-rich bulk regions; thereby forming a wear resistantpolymeric material.

In another embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) irradiating astarting material by ionizing radiation, wherein the starting materialis a mixture of polymeric materials, wherein the polymeric material hasa gradient of antioxidants containing Irganox® 1010-rich surface regionsand vitamin E-rich bulk regions; ii) heating the irradiated startingmaterial; iii) continue heating the irradiated material followingirradiation; and iv) cooling the heated polymeric material, therebyforming a wear resistant polymeric material.

In another embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: irradiating astarting material by ionizing radiation at an elevated temperature belowthe melt, wherein the starting material is a mixture of UHMWPE and anantioxidant from the Irganox® family; thereby forming a wear resistantpolymeric material.

In another embodiment, the invention provides medical implants made bylayered molding of wear resistant polymeric materials, wherein thepolymeric material is made by a process comprising the steps of: i)irradiating a starting material by ionizing radiation, wherein thestarting material is a polymeric material or a mixture of polymericmaterials, wherein the polymeric material is blended or doped with atleast one antioxidant or already has a gradient of antioxidant, whereinthe articular surfaces of the polymeric material contain one or moreantioxidants from Irganox® family and the bulk regions of the polymericmaterial contain at least one antioxidant from the Irganox® familyand/or another antioxidant; thereby forming a wear resistant polymericmaterial.

In another embodiment, the invention provides medical implants made bylayered molding of wear resistant polymeric materials, wherein thepolymeric material is made by a process comprising the steps of: i)irradiating a starting material by ionizing radiation, wherein thestarting material is a polymeric material or a mixture of polymericmaterials, wherein the polymeric material is blended or doped with atleast one antioxidant or already has a gradient of antioxidant, whereinthe articular surfaces of the polymeric material contain one or moreantioxidants from Irganox® family and the bulk regions of the polymericmaterial contain at least one antioxidant from the Irganox® familyand/or another antioxidant; ii) heating the irradiated starting materialto a temperature of about 120° C. or more; iii) continue heating theirradiated material following irradiation; and iv) cooling the heatedpolymeric material, thereby forming a wear resistant polymeric material.

In another embodiment, the invention provides medical implants made bylayered molding of wear resistant polymeric materials, wherein thepolymeric material is made by a process comprising the steps of: i)irradiating a starting material by ionizing radiation, wherein thestarting material is a polymeric material or a mixture of polymericmaterials, wherein the polymeric material is blended or doped with atleast one antioxidant or already has a gradient of antioxidant, whereinthe articular surfaces of the polymeric material contain one or moreantioxidants from Irganox® family and the bulk regions of the polymericmaterial contain at least one antioxidant from the Irganox® familyand/or another antioxidant; ii) heating the irradiated starting materialto a temperature of about 200° C. or more; iii) continue heating theirradiated material following irradiation; and iv) cooling the heatedpolymeric material, thereby forming a wear resistant polymeric material.

In another embodiment, the invention provides medical implantscomprising wear resistant polymeric materials, wherein the polymericmaterial is made by a process comprising irradiating a starting materialby ionizing radiation, wherein the starting material is a polymericmaterial or a mixture of polymeric materials, wherein the polymericmaterial is blended or doped with at least one antioxidant or alreadyhas a gradient of antioxidant, wherein the articular surfaces of thepolymeric material contain one or more antioxidants from Irganox® familyand the bulk region of the polymeric material contain a differentantioxidant and one or more antioxidants from the Irganox® family.

According to one aspect of the invention, the polymeric material isirradiated at a temperature of about 40° C., about 75° C., about 100°C., about 110° C., about 120° C., about 130° C., about 135° C., about140° C., about 145° C., about 150° C., about 155° C., about 160° C.,about 165° C., about 170° C., about 175° C., about 180° C., about 185°C., about 190° C., or about 195° C.

According to an aspect of the invention, heating after irradiation isused to homogenize the concentration of at least one antioxidant throughthe polymeric material or medical implant. Heating is clone below, at orabove the melting point of the polymeric material or specifically byhigh temperature melting. A benefit of the heating process can be thatthe concentration of residual free radicals is reduced.

According to another aspect of the invention, the heating is continuedfor at least for one minute, 10 minutes, 20 minutes, 30 minutes, onehour, two hours, five hours, ten hours, 24 hours, or more.

According to another aspect of the invention, the radiation dose isabout 25, about 50, about 60, about 65, about 75, about 100, about 125,about 150, about 175, or about 200 kGy.

According to another aspect of the invention, the Irganox® is Irganox®1010.

According to another aspect of the invention, the Irganox® concentrationis between 0.0001 and 50%; between 0.01 and 1%; between 0.01 and 0.1%;or 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09% or 0.1%.

According to another aspect of the invention, the antioxidantconcentration is between 0.0001 and 50%; between 0.01 and 5%; between0.1 and 5%; 0.1, 0.2, 0.3, 04, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2,1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.5, 3, 15, 4, 4.5, or 5%.

According to another aspect of the invention, the bulk antioxidant istocopherol, vitamin-E, or Irganox®.

According to another aspect of the invention, the bulk antioxidant is amixture of different Irganoxes; or a mixture of different tocopherolsand Irganoxes.

According to another aspect of the invention, the Irganox® containingarticular surface is about between 0.001 and 5 mm; about 1, 1.2, 1.4,1.6, 1.8, 2, 2.2, 2.4, 2.6, 2.8, 3, 3.5, 4, or 5 mm in thickness.

According to another aspect of the invention, the Irganox® containingarticular and backside surfaces are of equal thickness or differentthicknesses.

According to another aspect of the invention, the polymeric material ismelted after irradiation, machined after irradiation to form a preform,and the perform is annealed after irradiation, wherein the annealing iscarried out before machining the polymeric material.

In another embodiment, the invention provides methods of making amedical implant comprising a polymeric material, wherein the polymericmaterial is irradiated at a temperature of about 100° C. or about 120°C., wherein the polymeric material is machined to form the medicalimplant, and wherein the polymeric material is packaged and sterilized.

In another embodiment, the invention provides methods of making a wearresistant polymeric material comprising the steps of: i) irradiating astarting material by ionizing radiation, wherein the starting materialis a polymeric material or a mixture of polymeric materials, wherein thepolymeric material is blended with one or more antioxidant of Irganox®family and with or without vitamin E; ii) mechanically deforming theantioxidant-blended and irradiated polymeric material at an elevatedtemperature below the melting point; iii) heating theantioxidant-blended irradiated starting material to a temperature thatis below or above the melting point of the polymeric material; and iv)cooling the heated polymeric material, thereby forming a wear resistantpolymeric material.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the starting material is obtainedby a method comprising the steps of: i) blending one or more polymericmaterials; and ii) consolidating the blend by compression molding as asingle layer or as multiple layers containing different concentrationsand/or types of one or more antioxidants.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the starting material is obtainedby a method comprising the steps of: i) blending one or more polymericmaterials with at least one antioxidant; and ii) consolidating the blendby compression molding as a single layer or as multiple layerscontaining different concentrations and/or of one or more antioxidants.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the polymeric material isirradiated and mechanically deformed, wherein the mechanically deformedcrosslinked material is heated to a temperature of about 130° C., about135° C., about 150° C., or about 180° C.

In another embodiment, the invention provides methods of making a wearresistant polymeric material, wherein the mechanical deformation iscarried out to a compression ratio of about 2.0 at temperature that isbelow the melting point of the polymeric material.

Unless otherwise defined, all technical and scientific terms used hereinin their various grammatical forms have the same meaning as commonlyunderstood by one of ordinary skill in the art to which this inventionbelongs. Although methods and materials similar to those describedherein can be used in the practice or testing of the present invention,the preferred methods and materials are described below. In case ofconflict, the present specification, including definitions, willcontrol. In addition, the materials, methods, and examples areillustrative only and are not limiting.

Further features, objects, and advantages of the present invention areapparent in the claims and the detailed description that follows. Itshould be understood, however, that the detailed description and thespecific examples, while indicating preferred aspects of the invention,are given by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

These and other aspects of the invention will become apparent to theskilled artisan in view of the teachings contained herein.

The invention is further disclosed and exemplified by reference to thetext and drawings that follow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 through 12 illustrate examples (0 to 41) of processes, steps andconditions of various methods of making wear resistant polymericmaterials or medical devices.

FIG. 13 depicts a schematic of a complete coverage shield covering aUHMWPE construct.

FIG. 14 depicts the construct of FIG. 13 that has been bisected formicrotoming.

FIG. 15 shows the variation of the trans vinylene index as a function ofdistance for UHMWPE irradiated at room temperature.

FIG. 16 shows the variation of the trans vinylene index as a function ofdistance for UHMWPE irradiated at 125° C.

FIG. 17 shows the variation of the trans vinylene index as a function ofdistance for UHMWPE irradiated at 2 different temperature (25° C. and125° C.) and different complete (that is, full) coverage shieldthicknesses (1 mm, 9 mm, and 15 mm).

FIG. 18 depicts a UHMWPE construct covered with a 1 cm thick aluminumpartial shield (hole in center).

FIG. 19 depicts the construct of FIG. 18 that has been bisected formicrotoming.

FIG. 20 shows the variation of the trans vinylene index as a function ofdistance for irradiated UHMWPE.

FIG. 21 compares unradiated UHMWPE (panel a) to the partially-shieldUHMWPE (panel b) according to FIG. 18.

FIG. 22 depicts various exemplary shield geometries, which can be usedin various arrangements according to the invention, such as in FIG. 31.

FIG. 23 depicts the use of the present invention in the fabrication ofan acetabular liner of a hip prosthesis.

FIG. 24 depicts the use of the present invention in the fabrication of amobile bearing knee prosthesis (such as a rotating platform knee).

FIG. 25 depicts the use of the present invention in the fabrication of aknee meniscus prosthesis.

FIG. 26 depicts the use of the present invention in the fabrication of ashoulder meniscus prosthesis.

FIG. 27 depicts the use of the present invention in the fabrication of aspacer for a finger joint.

FIG. 28 depicts exemplary shield edge geometry's and the resultantirradiation penetration envelopes. One set of illustrations showsshields that fully block the radiation from the covered area, while theother set of illustrations shows shields that partially block theradiation from the covered area.

FIG. 29 is an illustration of the effect of a radiation shield on thedepth of penetration of electron radiation at 10 MeV.

FIG. 30 is a depiction of the “teardrop” electron penetration envelopesignature left by electron radiation as it travels through a polymer.

FIG. 31 illustrates the irradiation of a polymer preform using both aring-shaped and disc-shaped shield in sequence.

FIG. 32 illustrates an embodiment of partial coverage shielding asdescribed herein.

FIG. 33 illustrates an embodiment of complete coverage shielding asdescribed herein.

FIG. 34 illustrates another embodiment of complete coverage shielding asdescribed herein.

FIG. 35 shows work-to-failure of unirradiated and 100-kGy irradiatedUHMWPE melted at 300 and 320° C. as a function of time.

FIG. 36 shows weight loss of unirradiated UHMWPE melted at 280, 300,320, and 340° C. as a function of time.

FIG. 37 shows weight loss of 65-kGy irradiated UHMWPE melted at 280,300, 320, and 340° C. as a function of time.

FIG. 38 shows weight loss of 100-key irradiated UHMWPE melted at 280,300, 320, and 340° C. as a function of time.

FIGS. 39a-b depict freeze fractures surfaces of slab compression moldedGUR1050 UHMWPE (39 a) and compression molded UHMWPE after melting at300° C. in nitrogen for 5 hours (39 b).

FIG. 40 shows wear rate as a function of cross-link density for hightemperature melted and irradiated UHMWPE compared to irradiated UHMWPEsand UHMWPEs irradiated and melted below 200° C.

FIG. 41a illustrates cross-link density as a function of radiation dosein UHMWPE blends of Irganox® 1010. The dashed lines indicate theradiation dose required to obtain a crosslink density of 0.260 mol/dm³;the crosslink density of 100-kGy irradiated virgin UHMWPE. The numbersat the right side of the graph are the radiation dose values required toobtain this level of crosslinking in Irganox® 1010 blended UHMWPE as afunction of concentration.

FIG. 41b illustrates cross-link density as a function of radiation dosein UHMWPE blends of Irganox® 1076. The dashed lines indicate theradiation dose required to obtain a crosslink density of 0.260 mol/dm³;the crosslink density of 100-kGy irradiated virgin UHMWPE. The numbersat the right side of the graph are the radiation dose values required toobtain this level of crosslinking in Irganox® 1076 blended UHMWPE as afunction of concentration.

FIG. 41c illustrates cross-link density as a function of radiation dosein UHMWPE blends of Irganox® 1035. The dashed lines indicate theradiation dose required to obtain a crosslink density of 0.260 mol/dm³;the crosslink density of 100-kGy irradiated virgin UHMWPE. The numbersat the right side of the graph are the radiation dose values required toobtain this level of crosslinking in Irganox® 1035 blended UHMWPE as afunction of concentration.

FIG. 42a-b illustrates layered molding of UHMWPE with differentconcentrations of Irganox® 1010 (42 a); Irganox® profile of layeredmolded UHMWPE (42 b).

FIGS. 43a-d illustrates thin-section preparation from specimen block forFTIR analysis.

FIG. 44 shows Irganox® 1010 and vitamin E profiles as a function ofdepth in layered molded UHMWPE. Profiles are splined averages of threesections.

FIG. 45 shows vitamin E (alpha-tocopherol) and Irganox® indices as afunction of depth for a layered molded puck containing 1 wt % vitamin Eon one side and 0.1 wt % Irganox® on the other side.

FIGS. 46a-g shows schematic examples of obtaining preferentially surfacecross-linked regions by machining after layered molding. Darker colorshows regions with higher antioxidant concentration blended into thepolymer.

FIG. 47a-c shows examples of different antioxidant blend configurationsduring molding. Darker color shows regions with higher antioxidantconcentration blended into the polymer.

FIG. 48 shows schematic description of masking during extraction. Darkercolor shows regions with higher antioxidant concentration in thepolymer.

FIG. 49 shows concentration profile of powder and solvent blends ofIrganox® 1010 with UHMWPE.

FIGS. 50a-b shows oxidation profiles of accelerated aged irradiatedIrganox® 1010 blends.

FIG. 51 shows Irganox® 1010 concentration profiles of molded Irganox®blends of UHMWPE before and after extraction by boiling hexane.

FIG. 52 shows cross-link density as a function of radiation dose inUHMWPE blend of 0.1 wt % Irganox® 1010 and 0.1 wt % vitamin E. Thedashed line indicates the radiation dose required to obtain a cross-linkdensity of 0.260 mol/dm³; the crosslink density of 100-kGy irradiatedvirgin UHMWPE. The number at the bottom of the dashed line is theradiation dose required to obtain this level of crosslinking in thisblended UHMWPE.

FIG. 53 shows cross-link density as a function of radiation dose inUHMWPE blend of vitamin E. The vertical dashed lines indicate theradiation dose required to obtain a cross-link density of 0.260 mol/dm³;the crosslink density of 100-kGy irradiated virgin UHMWPE. The numbersat the right side of the graph are the radiation dose values required toobtain this level of crosslinking in vitamin E-blended UHMWPE as afunction of concentration.

FIG. 54 shows oxidation index as a function of depth after squalenechallenge and bomb aging of irradiated vitamin E blends.

FIG. 55 shows oxidation index as a function of depth after squalenechallenge and bomb aging of irradiated vitamin E blends.

FIG. 56 shows Irganox® 1010 index as a function of depth after dopingand doping/homogenization.

FIG. 57 illustrates Irganox® 1010 index as a function of depth afterdoping and doping/homogenization.

FIG. 58 illustrates Impact strength as a function of the percentage ofthe thickness of the surface crosslinked layer in surface crosslinkedUHMWPE.

FIGS. 59a-b illustrates the vitamin E profiles of homogenized surfacecrosslinked UHMWPE containing 1 wt %-0.05 wt % vitamin E blendsirradiated to 100 kGy (59 a) and 150 kGy (59 b).

FIG. 60 illustrates thermogravimetric curves of UHMWPE melted at 280,300, 320, 340 and 400° C. for 24 hours.

FIGS. 61a-c shows the terminal vinyl index as a function of melting timeat 280, 300 and 320° C., in comparison with CM UHMWPE that was notsubjected to high temperature melting (61 a). The dependence ofelongation-at-break on the terminal vinyl group index (61 b). Thedependence of the strain-hardening modulus, G, on the vinyl index (61c).

FIG. 62a-d shows mechanical and wear properties of high temperaturemelted GUR1050 UHMWPEs compared to compression molded (CM) GUR1050UHMWPE without high temperature melting as a function of vinyl index.

FIG. 63 shows the effect of crosslink density on the POD wear rate ofradiation crosslinked UHMWPEs. The solid symbols represent irradiatedand melted UHMWPE without high temperature melting (CISM). These sampleshave been melted at approximately 170° C. after irradiation for lessthan 5 hours. The open symbols are irradiated UHMWPEs with prior hightemperature melting.

FIGS. 64a-c shows the effect of crosslink density on theelongation-at-break (64 a), IZOD impact strength (64 b) and ultimatetensile strength (64 c) of radiation crosslinked UHMWPEs. The solidsymbols represent irradiated and melted UHMWPE without high temperaturemelting (CISM). The open symbols are irradiated UHMWPEs with prior hightemperature melting.

FIG. 65 shows the effect of the initial vinyl index before irradiationon the crosslink density of irradiated high temperature melted UHMWPEs.The solid symbols represent irradiated and melted UHMWPE without hightemperature melting (CISM). The open symbols are irradiated UHMWPEs withprior high temperature melting.

FIGS. 66a-b depicts post-hexane oxidation of accelerated aged 150-kGyirradiated virgin UHMWPE and 0.2 wt % vitamin E-blended UHMWPE with andwithout high temperature melting at 300 and 320° C. for 5 hours.Accelerated aging was performed at 70° C. for 14 days at 5 atm. ofoxygen (66 a). Accelerated aging was performed at 70° C. for 14 days at5 atm. of oxygen after squalene doping at 120° C. for 2 hours (66 b).

FIGS. 67a-f depict schematic of a generic tibial insert with regionscontaining different concentrations of antioxidant. For example, theshaded regions contain Irganox® 1010 at a low concentration such as 0.05wt % and the other regions contain higher concentration of antioxidantsuch as 1 wt % vitamin E.

FIGS. 68a-e depict schematic of a generic acetabular liner(crosssectional view) with surface regions containing a lowconcentration of antioxidant, where the surface region containing a lowamount of antioxidant can cover entirely or partially top surface of theimplant (68 a). Low concentration of antioxidant can be contained onboth the top and backside surfaces of the implant (68 b). In addition,low concentration of antioxidant can be contained on the top and/orbackside surfaces of the implant such that locking mechanisms can bemachined into regions with high concentration of antioxidant (68 c, 68d). Examples of surface regions (top view) with varying antioxidantconcentration (68 e).

FIG. 69 depicts schematic of a hip implant with a highly crosslinkedarticular surface made by direct compression molding of layers of apolymer blend with a high concentration of vitamin E and a polymer blendwith a low concentration of an antioxidant from the Irganox® family suchas Irganox® 1010.

FIGS. 70a-c show vitamin E concentration profiles of 0.5 wt % vitaminE-blended UHMWPE as a function of depth away from the surface afterextraction and irradiation, respectively (70 a); the wear rate as afunction of depth away from the surface of 0.5 wt % vitamin E-blendedUHMWPE after extraction and 150 kGy irradiation (70 b); and the wearrate as a function of depth away from the surface of 1 wt % vitaminE-blended UHMWPE after extraction and 150, 200, 250 and 300 kGyirradiation (70 c).

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides methods for making cross-linked, wear andoxidation resistant polymeric materials. The invention pertains tomethods of making medical implants containing cross-linked andantioxidant-containing tough and ductile polymers, and materialsobtainable thereby and used therewith also are provided.

This application describes that the use of antioxidants, such asvitamin-E, increases the ductility of UHMWPE even further by acting as aplasticizing agent. Also, the application discloses that the presence ofan antioxidant delays and/or prevents chain scissioning that can occurduring high temperature melting.

High Temperature Melting

The invention pertains to use the high temperature melting (HTM) incombination with radiation crosslinking and/or high pressurecrystallization in various sequences as outlined herein (see forexample, in FIGS. 1-12). One object of the invention is to achieving aUHMWPE with low wear, high oxidation resistance, and hightoughness/ductility.

Although not bound by any theory, it is believed that at hightemperatures two processes could affect the morphology and properties ofUHMWPE: One is the increased self-diffusion of chain entanglementsacross the granule boundaries and the other is the chain scissioning,which in turn would help self-diffusion. Inter-chain diffusion canincrease entanglements in the amorphous phase of UHMWPE, which can leadto increased elongation. Inter-chain diffusion is increased effectivelyabove the melting point of the crystals where the mobility of all chainsis increased and the crystalline phase is not present to inhibitmobility. Above the melting point of the crystals, increasingtemperature increases kinetic energy of the amorphous chains, resultingin more effective diffusion. Therefore, effective entanglement of thechains in the amorphous phases can be obtained by increasing temperatureand also by increasing the time allowed for inter-chain diffusion. Thisis also true for diffusion across the grain boundaries, which mayincrease the strength of the material considerably.

Un-crosslinked UHMWPE has shape memory when molten at typical processingtemperature, for example 150° C., for a moderate amount of time. This isbecause the diffusion of the ultra-high molecular weight chains of thepolymer is very slow and it is energetically favorable to assume for thechains (and crystals) mostly the same configuration during cooling andre-crystallization. However, the more diffusion is allowed for thechains, that is the higher the melting temperature and the longer themelting time, shape memory will be hindered and the polymer will notre-crystallize in the same configuration and to the same crystallinitylevel.

Radiation crosslinking reduces wear of UHMWPE, but residual freeradicals remain in UHMWPE, resulting in long-term oxidation. Theincorporation of an antioxidant such as vitamin E in UHMWPE canstabilize these residual free radicals and render the cross-linkedUHMWPE oxidatively stable without the need for quenching the freeradicals. According to one aspect of the invention, the antioxidant isincorporated in UHMWPE powder and molded or extruded together, and/orthe antioxidant is diffused into already molded or extruded parts beforeor after radiation crosslinking.

One approach to reduce free radicals in radiation cross-linked UHMWPE isto anneal below the melting point. Annealing below the melting point isdesirable because melting the crystals completely in the presence of thecross-links reduces the mechanical strength of the material through adecrease in crystallinity. Annealing below the melting point can be doneat an elevated temperature more effectively by increasing the pressure.This is because the inciting point of cross-linked UHMWPE increases withincreasing pressure. For example, it is observed that 100-kGy irradiatedUHMWPE is not completely molten at 150° C. under 10,000 psi ofhydrostatic pressure, whereas its melting point at ambient pressure isapproximately 140° C.

Another approach is to completely melt the crystals by annealing abovethe melting point. Depending on the pre-melting crystallinity and thecrosslink density of the network, which dictate the mobility of thechains, increasing the temperature during melting can increase theelongation, leading to higher toughness.

Yet, another approach to eliminate free radicals as well as increasingstrength of the cross-linked UHMWPE is high pressure crystallization andhigh pressure annealing. UHMWPE exhibits a hexagonal crystal phase athigh temperatures and pressures (above about 210 MPa and about 160° C.)where crystals can grow to a larger extent and overall crystallinity canbe increased. The polymer can be crystallized from the melt by firstmelting then increasing the pressure to a level such that extended chaingrowth is observed. The second approach (high pressure annealing) is topressurize and heat in such a manner that the hexagonal phase isachieved through the solid phases (orthorhombic, monoclinic or transienthexagonal) rather than the melt. In both of these approaches, the freeradicals are reduced or eliminated due to the mobility induced in thecrystals due to the phase transformation. In a similar manner,deformation of the crystalline material in the solid state by mechanicalloading can also result in mobility in the crystals and reduction orelimination in free radicals.

Extended chain crystal formation in UHMWPE can result in a UHMWPE withhigher crystallinity and mechanical strength. Increasing the elongationof a highly crystalline, high strength UHMWPE is also desirable. Thiscan be achieved by increasing the elongation of UHMWPE prior to highpressure crystallization.

Controlling the cross-link density and cross-link density distributionis possible by irradiation at different temperatures. For example,irradiation in the melt state can result in homogenous distribution ofcross-links in contrast to irradiation below the melting point, wherecross-links are not formed in the crystalline regions and only theamorphous content is cross-linked. Similarly, one can use a spatiallyvariable anti-crosslinking agent concentration such as that of vitamin Eduring irradiation to tailor the crosslink density distribution.

In one embodiment, virgin polymeric material or a blend of the polymericmaterial with an antioxidant such as vitamin E is melted above themelting point at a high temperature for a period of time (FIG. 1 at 0).

In another embodiment, virgin polymeric material or a blend of thepolymeric material with an antioxidant such as vitamin E is melted abovethe melting point at a high temperature for a prolonged period of time.Further, this high elongation material is pressure crystallized underlow or high pressure to obtain a highly crystalline material with highelongation. Then, this highly crystalline material with improvedelongation may be cross-linked by irradiation or chemical means (FIG. 2at 1 and 3, and FIG. 3 at 4). After radiation cross-linking, thematerial can be heated to below or above the melting point or above themelting point at a high temperature for a prolonged period of time (FIG.4 at 7 and 9). Alternatively, after cross-linking, it can be pressurecrystallized or annealed (FIG. 6 at 13 and 15).

In another embodiment, the starting material is a blend of polymericmaterial with a lower molecular weight polymer blend such that theeffective molecular weight between cross-links is reduced and thecrosslink density is increased compared to virgin UHMWPE at the sameradiation dose. In another embodiment, the starting material is a blendof UHMWPE with a lower molecular weight polymer blend such that theresultant UHMWPE is more lubricious and the coefficient of friction ofUHMWPE against CoCr is lower than that of virgin UHMWPE.

In another embodiment, melting a virgin polymeric material or a blend ofthe polymeric material with an antioxidant such as vitamin E above themelting point at a high temperature for a prolonged period time is usedto increase the elongation. This UHMWPE is deformed under load biaxiallyor uniaxially to obtain a highly oriented polymer (FIG. 2 at 2). Then,this material can be radiation crosslinked (FIG. 3 at 5 and 6). Aftercross-linking, the material can be heated to below or above the meltingpoint or above the melting point at a high temperature for a prolongedperiod of time (FIG. 4 at 8). Alternatively, after cross-linking, it canbe pressure crystallized or annealed (FIG. 6 at 14).

In another embodiment, melting a blend of polymeric material with anantioxidant such as vitamin E above the melting point at a hightemperature for a prolonged period time is used to increase theelongation. The material is then pressure crystallized or annealed.Then, it is cross-linked by radiation or chemical means. Finally, it isdiffused an antioxidant such as vitamin E by doping followed optionallyby homogenization of the antioxidant at elevated temperature (FIG. 5 at10 and 12).

In another embodiment, melting a virgin polymeric material or a blend ofthe polymeric material with an antioxidant such as vitamin E above themelting point at a high temperature for a prolonged period of time isused to increase the elongation. This UHMWPE is deformed under loadbiaxially or uniaxially to obtain a highly oriented polymer. Then, thismaterial is radiation crosslinked. Finally, it is diffused anantioxidant such as vitamin E by doping followed optionally byhomogenization of the antioxidant at elevated temperature (FIG. 5 at11).

In one embodiment, virgin polymeric material or a blend of the polymericmaterial with an antioxidant such as vitamin E is melted above themelting point at a high temperature for a prolonged period of time.Further, this high elongation material is pressure crystallized underlow or high pressure to obtain a highly crystalline material with highelongation. Then, this highly crystalline material with improvedelongation may be cross-linked by irradiation or chemical means. Afterradiation cross-linking, the material is deformed under load biaxiallyor uniaxially to obtain a highly oriented polymer (FIG. 7 at 16 and 18).The material may further be heated below or above the melting point orabove the melting point at a high temperature (FIG. 8 at 19 and 21).Alternatively, it may be pressure crystallized at low or high pressure(FIG. 8 at 23).

In one embodiment, virgin polymeric material or a blend of the polymericmaterial with an antioxidant such as vitamin E is melted above themelting point at a high temperature for a prolonged period of time. ThisUHMWPE is deformed under load biaxially or uniaxially to obtain a highlyoriented polymer. Further, it is cross-linked by radiation or chemicalmeans. It may further be deformed under load biaxially or uniaxially(FIG. 7 at 17). After deformation, it may be heated below or above themelting point or above the melting point at a high temperature (FIG. 8at 20). Alternatively, it may be pressure crystallized at low or highpressure (FIG. 8 at 24).

In one embodiment, virgin polymeric material or a blend of the polymericmaterial with an antioxidant such as vitamin E is melted above themelting point at a high temperature for a prolonged period of time. Thismaterial is further cross-linked by radiation or chemical means. It mayfurther be deformed under load biaxially or uniaxially. Afterdeformation, it may be heated below or above the melting point or abovethe melting point at a high temperature (FIG. 8 at 22). Alternatively,after deformation, it may be pressure crystallized at low or highpressure (FIG. 8 at 26).

In one embodiment, a virgin polymeric material or a blend of thepolymeric material with an antioxidant such as vitamin E is cross-linkedby radiation or chemical means. It is then heated above the meltingpoint at a high temperature for a prolonged period of time (FIG. 9 at27). This material may further be pressure crystallized at high or lowpressure (FIG. 9 at 28). Alternatively, after melting, it may bedeformed under load biaxially or uniaxially (FIG. 9 at 29).Alternatively, it may be diffused with an antioxidant by doping followedoptionally by homogenization of the antioxidant by annealing at elevatedtemperature (FIG. 9 at 30).

In one embodiment, a virgin polymeric material or a blend of thepolymeric material with an antioxidant such as vitamin E is melted abovethe melting point at a high temperature for a prolonged period of time.Then, this material is cross-linked by radiation or chemical means (FIG.10 at 31). The material can be further heated below or above the meltingpoint or above the melting point at a high temperature (FIG. 10 at 32).Alternatively, after cross-linking, it can be pressure crystallized atlow or high pressure (FIG. 10 at 33). Alternatively, aftercross-linking, it can be deformed under load uniaxially or biaxially(FIG. 10 at 34). An antioxidant such as vitamin E may be diffused intothe cross-linked UHMWPE by doping in antioxidant followed optionally byhomogenization of the antioxidant at elevated temperature FIG. 10 at(35).

In one embodiment, melting a virgin polymeric material or a blend of thepolymeric material with an antioxidant such as vitamin E above themelting point at a high temperature for a prolonged period time is usedto increase the elongation. The material is then cross-linked byradiation or chemical means. An antioxidant such as vitamin E can bediffused into this material by doping optionally followed byhomogenization at elevated temperature. The strength of this material isthen improved by high pressure crystallization or annealing (FIG. 11 at36).

In one embodiment, melting a virgin polymeric material or a blend of thepolymeric material with an antioxidant such as vitamin E above themelting point at a high temperature for a prolonged period time is usedto increase the elongation. The material is then cross-linked byradiation or chemical means. An antioxidant such as vitamin E can bediffused into this material by doping optionally followed byhomogenization at elevated temperature. The material can further bedeformed under load uniaxially or biaxially (FIG. 11 at 37).

In one embodiment, melting a virgin polymeric material or a blend of thepolymeric material with an antioxidant such as vitamin E above themelting point at a high temperature for a prolonged period time is usedto increase the elongation. The material is then cross-linked byradiation or chemical means. An antioxidant such as vitamin E can bediffused into this material by doping optionally followed byhomogenization at elevated temperature. It can further be heated belowor above the melting point or above the melting point at a hightemperature (FIG. 11 at 38).

In one embodiment virgin polymeric material or a blend of the polymericmaterial with an antioxidant such as vitamin E is cross-linked byradiation or chemical means. This material is then heated below or abovethe melting point or above the melting point at a high temperature. Itcan be further cross-linked by radiation or chemical means. Finally, itis pressure crystallized at high or low pressure (FIG. 12 at 39).

In one embodiment, a virgin polymeric material or a blend of thepolymeric material with an antioxidant such as vitamin E is cross-linkedby radiation or chemical means. This material is then heated below orabove the melting point or above the melting point at a hightemperature. It can be further cross-linked by radiation or chemicalmeans. Finally, it is deformed under load uniaxially or biaxially (FIG.12 at 40).

In one embodiment, a virgin polymeric material or a blend of thepolymeric material with an antioxidant such as vitamin E is cross-linkedby radiation or chemical means. This material is then heated below orabove the melting point or above the melting point at a hightemperature. It can be further cross-linked by radiation or chemicalmeans. Finally, it is diffused with an antioxidant such as vitamin E bydoping optionally followed by homogenization at an elevated temperature(FIG. 12 at 41).

Controlling Crosslink Density Distribution

In one embodiment, a blend of the polymeric material with a spatiallycontrolled concentration of blend is used as starting material. Forexample, UHMWPE powders containing different amount of vitamin E can beconsolidated such that some parts of the consolidated UHMWPE containsmore vitamin E than other parts. When this material is irradiated, thecrosslink density, thus the wear rate and mechanical properties of thesedifferent parts can be different. This is due to vitamin E inhibitingcross-linking in UHMWPE with increasing concentration. Alternatively,UHMWPE can be molded with a spatially controlled concentration of asecond component such as low molecular weight polyethylene. When thismaterial is irradiated, the crosslink density, thus the wear rate andmechanical properties of these different parts can be different.Alternatively, spatially controlled distribution of one or more freeradical scavenger/antioxidant other than vitamin E is used.

In another embodiment, gradient crosslinking in UHMWPE can be used byusing shields against irradiation in a desired pattern. Alternatively, achemical crosslinking species can be used in only part of the UHMWPE forthe same purpose.

Melting at high temperature for prolonged periods of time enhances thediffusion of polymer chains in polyethylene and other high molecularweight polymers, increasing the strength of the polymer throughincreased entanglements. At the same time, increasing temperatureincreases degradation of the polymer chains through chain scissioningand this decreases the mechanical properties of the material. Therefore,these two factors are in competition in terms of the strength of thepolymer.

Wear resistance in UHMWPE as a joint bearing surface has directlyrelated to reduced plastic deformation. Cross-linking by radiation orchemical means decreases the plastic deformation and decreases the wear.This is because wear fibrils are a result of the orientation of polymerfibrils in the principal direction of motion and their weakening andfracture in the transverse directions. Wear is then caused bymultidirectional motion.

By high temperature melting and increasing the entanglements betweenchains, wear resistance can be increased. Therefore, radiation/chemicalcrosslinking can be used in conjunction with high temperature melting toincrease the wear resistance of UHMWPE as a bearing surface. However,when a high temperature melted UHMWPE is irradiated, it is not oxidationresistant and the free radicals have to stabilized or eliminated foroxidative stability.

The oxidation resistance of radiation cross-linked UHMWPE is crucial inits performance as a bearing surface as oxidation deteriorates itsmechanical and wear properties in vivo over a long period of time.Oxidation is largely thought to be related to residual free radicalstrapped in the crystalline regions of the polymer, their migration tothe crystalline/amorphous interface and their reaction with diffusedoxygen. Oxidation may also be related to other free radical generatingmechanisms such as the material coming into contact with a free radicalinducing medium or chains scission through static, dynamic or cyclicdeformation. The safest way of protecting against these free radicals isthe introduction of an antioxidant such as vitamin E into UHMWPE beforeor after cross-linking.

An antioxidant with a lipophilic structure can also act as aplasticizing agent in addition to protecting the material againstoxidation. Then, it would be advantageous to incorporate the antioxidantin the polymer to improve mechanical properties as well.

In the case of high temperature melting, it is herein demonstrated thatchain scission dominates as temperature is increased. The inclusion ofan antioxidant/free radical scavenger can decrease the breakdown of thematerial and also affect its cross-linking ability with subsequentprocessing steps.

Antioxidants/free radical scavengers/anti-crosslinking agents can bechosen from but not limited to glutathione, lipoic acid, vitamins suchas ascorbic acid (vitamin C), vitamin B, vitamin D, vitamin-E,tocopherols (synthetic or natural, alpha-, gamma-, delta-), acetatevitamin esters, water soluble tocopherol derivatives, tocotrienols,water soluble tocotrienol derivatives; melatonin, carotenoids includingvarious carotenes, lutein, pycnogenol, glycosides, trehalose,polyphenols and flavonoids, quercetin, lycopene, lutein, selenium,nitric oxide, curcuminoids, 2-hydroxytetronic acid; cannabinoids,synthetic antioxidants such as tertiary butyl hydroquinone,6-amino-3-pyrodinoles, butylated hydroxyanisolc, butylatedhydroxytoluene, ethoxyquin, tannins, propyl gallate, other gallates,Aquanox family; Irganox® and Irganox® B families including Irganox®1010, Irganox® 1076, Irganox® 1330, Irganox® 1035; Irgafos® family;phenolic compounds with different chain lengths, and different number ofOH groups; enzymes with antioxidant properties such as superoxidedismutase, herbal or plant extracts with antioxidant properties such asSt. John's Wort, green tea extract, grape seed extract, rosemary,oregano extract, mixtures, derivatives, analogues or conjugated forms ofthese. They can be primary antioxidants with reactive OH or NH groupssuch as hindered phenols or secondary aromatic amines, they can besecondary antioxidants such as organophosphorus compounds orthiosynergists, they can be multifunctional antioxidants,hydroxylamines, or carbon centered radical scavengers such as lactonesor acrylated bis-phenols. The antioxidants can be selected individuallyor used in any combination. Also, antioxidants can be used inconjunction with hydroperoxide decomposers.

In an embodiment, the polymer blend is irradiated at a dose rate ofabout 1 to 1000 kGy per pass. The irradiation dose rates that can bereached with electron beam are much higher than those with gammairradiation. Electron beam dose rate are typically on the order of 1 toseveral hundred kGy per pass with each pass taking anywhere between afew seconds to a few minutes. E-beam irradiation is performed by passingthe UHMWPE under the beam. In each pass a quantifiable dose is applied.The close/pass could be the entire desired dose or a fraction thereof.In some embodiments the decision for the dose/pass is made to avoidoverheating (for instance complete melting) of UHMWPE. In others thedose/pass is determined based on the desired properties that onetargets. The dose/pass could be 1/10, 1/9, 1/8, 1/7, 1/6, 1/5 etc. . . .of the total desired dose level. Also the dose received at each passduring an irradiation run need not to be equal each other; anycombination of dose/pass values could be used to reach the total targetdose. The same approach is used with gamma irradiation, which involvespassing UHMWPE in front of the gamma source.

The polymer blend is brought to a certain initial temperature andirradiated. The dose rate is high enough to cause radiation generatedheating (including adiabatic and partially adiabatic) of the polymer.The temperature of the sample during irradiation depends on the startingtemperature and the radiation dose level used. Following equation, whichassumes purely radiation generated heating (including adiabatic andpartially adiabatic) conditions, can be used to estimate thetemperature:D=ΔH _(m,i)(T _(i))+c _(p) ΔT,  EQ1:where D is the radiation dose level absorbed by the sample, T_(i) is theinstantaneous temperature of the sample, ΔT (=T_(i)−T_(o)) is thedifference between the instantaneous temperature (T_(i)) of the sampleand the initial temperature (T_(o)) of the sample, ΔH_(m,i)(T_(i)) isthe melting enthalpy of the crystals that melt below the instantaneoustemperature of the sample, and c_(p) is the specific heat of thepolymer. This equation assumes purely radiation generated heating(including adiabatic and partially adiabatic) conditions; while therewill be some heat loss to the surroundings near the surface of theirradiated sample, the bulk of the sample will more closely follow thetemperature predicted by this equation, especially at high dose rates,and thus is a practical approximation. If a certain temperature isdesired during irradiation, the equation is used to determine theirradiation parameters. In this embodiment the radiation dose level canbe above 1 kGy. More preferably it can be 25 kGy, 50 kGy, 100 kGy, 150kGy, 200 kGy or above. The dose rate can be about 1, 10, 25, 75, 100,150, 200, or more kGy per pass or any dose rate in-between. The initialtemperature can be below room temperature (RT), RT, above RT, about 40,50, 75, 100, 110, 125, 130, 135° C. or more or any temperaturethereabout or therebetween. The irradiation can be carried out withe-beam, gamma, or x-rays. The latter two has lower dose rates thane-beam; therefore e-beam is more practical to reach high dose rates.

In another embodiment, the polymer blend is irradiated with gamma ore-beam followed by annealing or melting to recombine the free radicalstrapped in the crystalline domains. When the irradiation is carried outat low temperatures and/or low dose rates, the cross-link density islower than it is after the irradiated polymer blend is annealed belowthe melting point or melted.

In certain embodiments, it is not desired to completely melt the polymerblend during the irradiation step. For example, with a required highdose level (higher than 100 kGy) to reach a desired cross-link density,the polymer blend could be subjected to radiation generated (includingadiabatic and partially adiabatic) melting and result in completemelting of the blend. Post-irradiation melting reduces the crystallinityof the sample, which in turn reduces mechanical properties of the blend.One can prevent complete melting of the blend during irradiation bykeeping the dose rate low to minimize radiation generated heating(including adiabatic and partially adiabatic), reduce the initialtemperature, and/or reduce the radiation dose. In certain embodimentsthe polymer blend may require a higher initial temperature; in suchcases one can use low radiation dose rate to reduce the extent ofmelting by radiation generated heating.

In another embodiment, irradiation is carried out in multiple steps soas to reduce the extent of radiation generated heating (includingadiabatic and partially adiabatic) of the polymer blend. For instance,the polymer blend is irradiated in multiple passes under or near theradiation source (such as c-beam, gamma, or x-rays). The time betweenthe passes can be adjusted to allow the polymer blend to cool down tothe desired irradiation temperature. In some embodiments it is desirableto heat the sample between irradiation passes.

In another embodiment, the initial temperature of the polymer sample isadjusted such that the temperature of the polymer blend is increased toits peak melting point during irradiation.

DSC testing of warm irradiated blends typically exhibit three meltingpeaks on their first heat and two melting peaks on their second heat.The area under the highest melting peak of the first heat can be used todetermine the extent of melting in the polymer during warm irradiation.

In another embodiment, crystallinity of a blend of a polymeric materialwith at least one antioxidant is increased through, for example highpressure crystallization. The highly crystalline blend is thenirradiated. The crystalline domains contain little or no antioxidant, asa result, the free radicals formed in the crystalline domains are viablefor recombination and cross-linking reactions. To allow therecombination of the free radicals in the crystalline domains the blendis irradiated with a high enough dose rate to partially melt thepolymer. Alternatively, the irradiation is carried out at an elevatedtemperature to partially melt the polymer. Another approach is topost-irradiation anneal or melt the polymer to allow the free radicalsin the crystalline domains to recombine with each other. Theseapproaches result in an improved cross-linking efficiency for the blend.A post-irradiation homogenization step may be necessary to diffuse atleast one antioxidant from antioxidant-rich regions to antioxidant-poorregions.

In another embodiment, a polymer/antioxidant blend is mixed with virginpolymer flakes and consolidated. The consolidation cycle is kept asshort as possible and at the lowest possible temperature to minimizebleeding of the antioxidant from the antioxidant blended flakes intovirgin flakes. The consolidated polymer is then irradiated andsubsequently homogenized to allow diffusion of antioxidant fromantioxidant-rich regions to antioxidant-poor regions.

Alternatively, the antioxidant doped flakes could be subjected to anannealing cycle to diffuse the antioxidant to deeper into individualflakes and minimize its presence as a surface coating. This also reducesthe extent of antioxidant bleeding across from the doped flakes tovirgin flakes during consolidation and/or irradiation.

The invention provides various methods to improve the oxidativestability of irradiated antioxidant-containing polymers. In anembodiment, the invention provides methods to improve oxidativestability of polymers by heat treatment (such as annealing) ofirradiated polymer-antioxidant blend to reduce the concentration of theresidual free radicals through recombination reactions resulting incross-linking and/or through reaction of the residual free radicals withthe antioxidant. The latter is likely to take place by the abstractionof a hydrogen atom from the antioxidant molecules to the polymer, thuseliminating the residual free radical on the polymer backbone. Henceheat treatment (such as annealing) of an irradiated polymer in thepresence of an antioxidant is more effective in reducing theconcentration of residual free radicals than heat treatment (such asannealing) of an irradiated polymer in the absence of an antioxidant.

In another embodiment, invention provides methods to improve oxidativestability of polymers by diffusing more antioxidant into the irradiatedpolymer-antioxidant blend. The antioxidant diffusion methods have beendescribed by Muratoglu et al. (see, e.g., US 2004/0156879; U.S.application Ser. No. 11/465,544, filed Aug. 18, 2006; PCT/US2006/032329Published as WO 2007/024689, which are incorporated herein byreference).

In another embodiment, invention provides methods to improve oxidativestability of polymers by extracting antioxidants and creating a gradientof antioxidant concentration. The antioxidant extraction methods havebeen described in WO 2008/092047, the methodologies of which are herebyincorporated by reference.

In another embodiment, invention provides methods to improve oxidativestability of polymers by mechanically deforming the irradiatedantioxidant-containing polymers to reduce or eliminate the residual freeradicals. Mechanical deformation methods have been described byMuratoglu et al. (see, e.g., US 2004/0156879; US 2005/0124718; andPCT/US05/003305 published as WO 2005/074619), which are incorporatedherein by reference.

The present invention also describes methods that allow reduction in theconcentration of residual free radical in irradiated polymer, even toundetectable levels, without heating the material above its meltingpoint. This method involves subjecting an irradiated sample to amechanical deformation that is below the melting point of the polymer.The deformation temperature could be as high as about 135° C., forexample, for UHMWPE. The deformation causes motion in the crystallinelattice, which permits recombination of free radicals previously trappedin the lattice through cross-linking with adjacent chains or formationof trans-vinylene unsaturations along the back-bone of the same chain.If the deformation is of sufficiently small amplitude, plastic flow canbe avoided. The percent crystallinity should not be compromised as aresult. Additionally, it is possible to perform the mechanicaldeformation on machined components without loss in mechanical tolerance.The material resulting from the present invention is a cross-linkedpolymeric material that has reduced concentration of residuals freeradical, and preferably substantially no detectable free radicals, whilenot substantially compromising the crystallinity and modulus.

The present invention further describes that the deformation can be oflarge magnitude, for example, a compression ratio of 2 in a channel die.The deformation can provide enough plastic deformation to mobilize theresidual free radicals that are trapped in the crystalline phase. Italso can induce orientation in the polymer that can provide anisotropicmechanical properties, which can be useful in implant fabrication. Ifnot desired, the polymer orientation can be removed with an additionalstep of heating at an increased temperature below or above the meltingpoint.

According to another aspect of the invention, a high strain deformationcan be imposed on the irradiated component. In this fashion, freeradicals trapped in the crystalline domains likely can react with freeradicals in adjacent crystalline planes as the planes pass by each otherduring the deformation-induced flow. High frequency oscillation, such asultrasonic frequencies, can be used to cause motion in the crystallinelattice. This deformation can be performed at elevated temperatures thatis below the melting point of the polymeric material, and with orwithout the presence of a sensitizing gas. The energy introduced by theultrasound yields crystalline plasticity without an increase in overalltemperature.

The present invention also provides methods of further heating followingfree radical elimination below melting point of the polymeric material.According to one aspect of the invention, elimination of free radicalsbelow the melt is achieved either by the sensitizing gas methods and/orthe mechanical deformation methods. Further heating of cross-linkedpolymer containing reduced or no detectable residual free radicals isdone for various reasons, for example:

1. Mechanical deformation, if large in magnitude (for example, acompression ratio of two during channel die deformation), will inducemolecular orientation, which may not be desirable for certainapplications, for example, acetabular liners. Accordingly, formechanical deformation:

a) Thermal treatment below the melting point (for example, less thanabout 137° C. for UHMWPE) is utilized to reduce the amount oforientation and also to reduce some of the thermal stresses that canpersist following the mechanical deformation at an elevated temperatureand cooling down. Following heating, it is desirable to cool down thepolymer at slow enough cooling rate (for example, at about 10° C./hour)so as to minimize thermal stresses. If under a given circumstance,annealing below the melting point is not sufficient to achieve reductionin orientation and/or removal of thermal stresses, one can heat thepolymeric material to above its melting point.

b) Thermal treatment above the melting point (for example, more thanabout 137° C. for UHMWPE) can be utilized to eliminate the crystallinematter and allow the polymeric chains to relax to a low energy, highentropy state. This relaxation leads to the reduction of orientation inthe polymer and substantially reduces thermal stresses. Cooling down toroom temperature is then carried out at a slow enough cooling rate (forexample, at about 10° C./hour) so as to minimize thermal stresses.

2. The contact before, during, and/or after irradiation with asensitizing environment to yield a polymeric material with nosubstantial reduction in its crystallinity when compared to thereduction in crystallinity that otherwise occurs following irradiationand subsequent or concurrent melting. The crystallinity of polymericmaterial contacted with a sensitizing environment and the crystallinityof radiation treated polymeric material is reduced by heating thepolymer above the melting point (for example, more than about 137° C.for UHMWPE). Cooling down to room temperature is then carried out at aslow enough cooling rate (for example, at about 10° C./hour) so as tominimize thermal stresses.

As described herein, it is demonstrated that mechanical deformation caneliminate residual free radicals in a radiation cross-linked UHMWPE. Theinvention also provides that one can first deform UHMWPE to a new shapeeither at solid- or at molten-state, for example, by compression.According to a process of the invention, mechanical deformation ofUHMWPE when conducted at a molten-state, the polymer is crystallizedunder load to maintain the new deformed shape. Following the deformationstep, the deformed UHMWPE sample is irradiated below the melting pointto cross-link, which generates residual free radicals. To reduce thesefree radicals to as low as undetectable levels, the irradiated polymerspecimen is heated to a temperature below the melting point of thedeformed and irradiated polymeric material (for example, up to about135° C. for UHMWPE) to allow for the shape memory to partially recoverthe original shape. Generally, it is expected to recover about 80-90% ofthe original shape. During this recovery, the crystals undergo motion,which can help the free radical recombination and elimination. The aboveprocess is termed as a ‘reverse-IBMA’. The reverse-IBMA(reverse-irradiation below the melt and mechanical annealing) technologycan be a suitable process in terms of bringing the technology tolarge-scale production of UHMWPE-based medical devices.

The consolidated polymeric materials according to any of the methodsdescribed herein can be irradiated at room temperature or at an elevatedtemperature below or above the melting point of the polymeric material.

In certain embodiments of the present invention any of the method stepsdisclosed herein, including blending, mixing, consolidating, quenching,irradiating, annealing, mechanically deforming, doping, homogenizing,heating, melting, and packaging of the finished product, such as amedical implant, can be carried out in presence of a sensitizing gasand/or liquid or a mixture thereof, inert gas, air, vacuum, and/or asupercritical fluid.

The consolidated and irradiation cross-linked polymeric materialsaccording to any of the methods described herein can be further dopedwith an antioxidant.

The consolidated and irradiation cross-linked polymeric materialsaccording to any of the methods described herein can be further dopedwith an antioxidant and homogenized at a temperature below or above themelting point of the polymeric material.

In another embodiment, the invention provides a partially or entirelyhighly cross-linked, oxidatively stable highly crystalline medicaldevice, made by any of the above methods.

In another embodiment, the invention provides a partially or entirelyhighly cross-linked, oxidatively stable highly crystalline medicaldevice, wherein the polymeric material is machined subsequently afterthe consolidation, irradiation, heating and/or annealing or thequenching step.

In another embodiment, the invention provides a highly cross-linked,oxidatively stable highly crystalline medical device.

According to an aspect of the invention, the limitations of antioxidantdiffusion in polymeric material are overcome by shortening the diffusionpath of antioxidant necessary after irradiation. This is achieved bycreating a polymeric article that has higher antioxidant concentrationin the bulk (generally the interior regions) and lower antioxidantconcentration on the surface (exterior regions). When this polymericarticle is irradiated, the antioxidant rich regions in the bulk, inwhich wear reduction through cross-linking is not necessary, have alower final cross-link density than they would have in the absence orlessened presence of antioxidant. On the other hand, the surfacecontains either no antioxidant or lower concentrations of antioxidant.Therefore, the surface is cross-linked during irradiation to levelssimilar to material irradiated in the absence of antioxidant and thewear rate is reduced. Cross-linking is only needed on and near thearticular surfaces to improve the wear resistance of the implant.Although the surface and the bulk of a polymeric material generallyrefer to exterior regions and the interior regions, respectively, theregenerally is no discrete boundary between these two regions. The regionsare more of a gradient-like transition, can differ based upon the sizeand shape of the object and the resin used.

Irradiation of UHMWPE with antioxidant/anti-crosslinking agents such asvitamin E reduces the cross-linking efficiency of polymeric material andalso reduces the antioxidant potency of the antioxidant(s). Still, insome embodiments, there is enough antioxidant in the bulk such thatafter the irradiation step(s) there is still enough antioxidant potencyto prevent oxidation in the bulk of the polymeric material. Thus, afterirradiation, the polymeric article is oxidation-resistant in the bulkand is highly cross-linked on the surface. However, the surface maystill contain unstabilized free radicals that can oxidize without enoughantioxidant and reduce the mechanical properties of the article.Alternatively, even if a gradient vitamin E/antioxidant concentration isnot present, some antioxidant may be used up during the processing stepssuch as heating or irradiation and oxidative stability may be decreasedor compromised. To prevent oxidation on the antioxidant-poor surfaceregion, the article can be irradiated at an elevated temperature belowor above the melting point to reduce the concentration of residual freeradicals. Or the irradiated article can be treated by using one or moreof the following methods:

(1) doping with α-tocopherol through diffusion at an elevatedtemperature below or above the melting point of the irradiated polymericmaterial followed optionally by homogenization;

(2) mechanically deforming of the UHMWPE followed by heating below orabove the melting point of the article;

(3) high pressure crystallization or high pressure annealing of thearticle; and

(4) further heat treating the article below or above the melting point.

After one or more of these treatments, the free radicals are stabilizedor practically eliminated (reduced to undetectable or insignificantlevels) in the article.

Another added benefit of this invention is that the α-tocopherol dopingcan be carried out at elevated temperatures to shorten the diffusiontime.

All of the embodiments are described with α-tocopherol as theantioxidant but any other antioxidant/free radical scavenger or mixturesof antioxidants/free radical scavengers also can be used.

According to one embodiment, the polymeric material is an article havinga shape of an implant, a preform that can be machined to an implantshape, or any other shape.

In one embodiment, the polymeric article is prepared withantioxidant/anti-crosslinking agent-rich andantioxidant/anti-crosslinking agent-poor regions where theantioxidant/anti-crosslinking agent-poor regions are located at one ormore of the surface (exterior regions) and theantioxidant/anti-crosslinking agent-rich regions are in the bulk(generally the interior regions).

An advantage of starting with antioxidant/anti-crosslinking agent-richand antioxidant/anti-crosslinking agent-poor regions in the polymericarticle is that the radiation cross-linking is primarily be limited tothe antioxidant/anti-crosslinking agent-poor regions (in mostembodiments the articular surfaces) and therefore the reduction in themechanical properties of the implant due to cross-linking is minimized.

In another embodiment, the consolidated polymeric material is fabricatedthrough direct compression molding (DCM). The DCM mold is filled with acombination of polyethylene resin, powder, or flake containingα-tocopherol and with virgin polyethylene resin, powder, or flake, whichis without antioxidant/anti-crosslinking agent. The mold is then heatedand pressurized to complete the DCM process. The concentration ofantioxidant/anti-crosslinking agent in the initialantioxidant/anti-crosslinking agent-containing resin, powder, or flakemay be sufficiently high to retain its (their) efficiency throughout theDCM process, and any subsequent irradiation and cleaning steps. In theantioxidant/anti-crosslinking agent-poor regions, the totalconcentration of antioxidant/anti-crosslinking agent is between about0.0005 wt % and about 20 wt % or higher, preferably between about 0.005wt % and about 5.0 wt %, preferably about 0.05 wt %, or preferably about0.1 wt %. In the antioxidant/anti-crosslinking agent-rich regions, thetotal concentration of antioxidant/anti-crosslinking agent is betweenabout 0.0005 wt % and about 20 wt % or higher, preferably between about0.005 wt % and about 5.0 wt %, preferably about 1 wt %, or preferablyabout 2 wt %. The DCM mold is filled with either or both of the resins,powders, or flakes to tailor the distribution of theantioxidant/anti-crosslinking agent in the consolidated polymericarticle. One issue is the diffusion of antioxidant/anti-crosslinkingagent from the blended resin, powder, or flake regions to the virginresin, powder, or flake regions, especially during consolidation wherehigh temperatures and durations are typical. Any such diffusion wouldreduce the efficiency of subsequent cross-linking in the affected virginresin, powder, or flake regions. One can control the diffusion processby tailoring the distribution of antioxidant/anti-crosslinking agent, byoptimizing the type and content of antioxidant/anti-crosslinking agentin the rich and poor regions of the blended polymer, by reducing thetemperature of consolidation, and/or reducing the time of consolidation.

In some embodiments, the antioxidant/anti-crosslinking agent-rich regionis predominantly confined to the core of the polymeric article and theantioxidant/anti-crosslinking agent-poor polymeric material ispredominantly confined to the outer shell whereby the thickness of theα-tocopherol-poor region is between about 0.01 mm and 20 mm, morepreferably between about 1 mm and 5 mm, or more preferably about 3 mm.

In some embodiments, the outer layer is limited to only one or morefaces of the polymeric article. For example a polymeric article is madethrough DCM process by compression molding two layers of polyethyleneresin, powder, or flake, one containing 0.3 or 0.5 wt % a-tocopherol andone virgin with no α-tocopherol. The order in which the two resins,powders, or flakes are placed into the mold determines which faces ofthe polymeric article are α-tocopherol poor and the thickness of theα-tocopherol-poor region is determined by the amount of virgin resin,powder, or flake used. This polymeric article is subsequentlyirradiated, doped with α-tocopherol, homogenized, machined on one ormore of the faces to shape a polymeric implant, packaged and sterilized.Alternatively, the polymeric article containingantioxidant/anti-crosslinking agent-rich andantioxidant/anti-crosslinking agent-poor regions is irradiated, thenhomogenized, machined on one or more of the faces to shape a medicalimplant, packaged and sterilized.

In some embodiments, the antioxidant/anti-crosslinking agent-rich regionis molded from a blend of antioxidant/anti-crosslinking agent-containingresin, powder, or flake and virgin polyethylene resin, powder, or flake.

In some embodiments, the resin, powder, or flake containingantioxidant/anti-crosslinking agent and the virgin polyethylene resin,powder, or flake are dry-mixed prior to molding, thereby creating adistribution of antioxidant/anti-crosslinking agent-rich andantioxidant/anti-crosslinking agent-poor regions throughout thepolymeric article.

In some embodiments, the antioxidant/anti-crosslinking agent-poorpolymeric region is confined to the articular bearing surface of theimplant.

In some embodiments, the resin, powder, or flake containingantioxidant/anti-crosslinking agent undergoes partial or completeconsolidation prior to the DCM process. This preformed piece ofantioxidant/anti-crosslinking agent-containing polymeric material allowsmore precise control over the spatial distribution ofantioxidant/anti-crosslinking agent in the finished part. For example,the partially or completely consolidated resin, powder, or flake isplaced in a mold surrounded by virgin resin, powder, or flake andfurther consolidated, creating a polymeric article with anantioxidant/anti-crosslinking agent-poor region on the outer shell andantioxidant/anti-crosslinking agent-rich region in the bulk of thepolymeric article.

In another embodiment a polymeric component is fabricated through DCM asdescribed above with spatially-controlled antioxidant/anti-crosslinkingagent-rich and antioxidant/anti-crosslinking agent-poor regions. Thiscomponent is subsequently treated by e-beam irradiation. E-beamirradiation is known to have a gradient cross-linking effect in thedirection of the irradiation, but this is not always optimized incomponents which have curved surfaces, such as acetabular cups, wherethe cross-linking is different at different points on the articulatingsurface. The spatial distribution of antioxidant/anti-crosslinkingagent-rich regions is used in conjunction with e-beam irradiation tocreate uniform surface cross-linking which gradually decreases tominimal cross-linking in the bulk. After irradiation, the polymericcomponent is doped with at least one antioxidant. This component iscross-linked and stabilized at the surface and transitions to theuncross-linked and stabilized material with increasing depth from thesurface.

In some embodiments the antioxidant/anti-crosslinking agent/polymericmaterial blended resin, powder, or flake mixture has a very highantioxidant/anti-crosslinking agent concentration such that when thisresin, powder, or flake mixture is consolidated with neat resin, powder,or flake there is a steep gradient of antioxidant/anti-crosslinkingagent across the interface. The consolidated piece is then irradiated tocross-link the polymer preferably in the antioxidant/anti-crosslinkingagent-poor region. Subsequently, the piece is heated to drive diffusionof at least one antioxidant from the antioxidant-rich bulk region to theantioxidant-poor surface region.

In some embodiments, a vitamin-E-polymeric material (for example,UHMWPE) blend and antioxidant/anti-crosslinking agent-poor polymericresin, powder, or flake are molded together to create an interface. Thequantities of the blend and/or the virgin resins are tailored to obtaina desired antioxidant/anti-crosslinking agent-poor polymeric materialthickness. Alternatively, the molded piece/material is machined toobtain the desired thickness of the antioxidant/anti-crosslinkingagent-poor polymeric layer. The machined-molded piece/material isirradiated followed by:

-   -   Either doping with vitamin E and homogenized below the melting        point of the polymeric material,    -   or heated below the melt without doping to reduce the free        radicals to as low as undetectable levels (for example, for        different durations),    -   or heated below the melt for long enough duration, to diffuse        the bulk antioxidant from the blend layer into the        antioxidant-poor layer (for example, for different durations,        different blend compositions are used to accelerate the        diffusion from the blend region to the antioxidant-poor region),    -   or heated to a temperature above the melting point to reduce        free radicals to as low as undetectable levels and/or improve        toughness,    -   or high pressure crystallized/annealed, thereby forming a        medical implant and/or device. The medical device can be used at        this stage or can be machined further to obtain a net shaped        implant. The device/implant also can be packaged and sterilized.

In another embodiment, the thickness of theantioxidant/anti-crosslinking agent-poor surface is determined by thefinal toughness of the polymeric material with a gradient crosslinkdensity. For example, a polymeric material with a crosslinked surfacelayer thickness of 1 mm in a 6 mm-thick polymeric material has highertoughness that one with a crosslinked surface layer thickness of 2 mm.

A low threshold in the initial concentration profile of theantioxidant/anti-crosslinking agent in the consolidated polymericmaterial is determined below which the regions are designated as surfacelayers and a high threshold above which the regions are designated asbulk layers. These two thresholds can be the same or they can bedifferent. In the case where they are different, the regions with valuesbetween these two thresholds are designated as the gradient interface.

Similarly, after radiation crosslinking, a low threshold in thecrosslink density or wear rate profile is determined below which theregions are designated as low crosslinking and a high threshold isdetermined above which the regions are designated as highly crosslinked.The regions with values between these two thresholds are designated asthe crosslink gradient.

In another embodiment, the antioxidant-doped or -blended polymericmaterial is homogenized at a temperature below the melting point of thepolymeric material for a desired period of time, for example, theantioxidant-doped or -blended polymeric material is homogenized forabout an hour to several days to one week or more than one week at roomtemperature to about 135° C. to 137° C. (for example for UHMWPE).Preferably, the homogenization is carried out above room temperature,preferably at about 90° C. to about 135° C., more preferably about 80°C. to about 100° C., more preferably about 120° C. to about 125° C.,most preferably about 130° C.

In another embodiment, the antioxidant-doped or -blended polymericmaterial is homogenized at a temperature above the melting point of thepolymeric material for a desired period of time, for example, theantioxidant-doped or -blended polymeric material is homogenized forabout an hour to several days to one week or more than one week at roomtemperature to about 300° C. Preferably, the homogenization is carriedout at about 140° C. to about 350° C., more preferably about 170° C. toabout 300° C., more preferably about 280° C. to about 300° C., mostpreferably about 300° C.

A purpose of homogenization is to make the concentration profile of atleast one additive throughout the interior of a consolidated polymericmaterial more spatially uniform. After doping of the polymeric materialis completed, the consolidated polymeric material is removed from thebath of antioxidant and wiped thoroughly to remove excess antioxidantfrom the surfaces of the polymeric material. The polymeric material iskept in an inert atmosphere (nitrogen, argon, and/or the like) or in airduring the homogenization process. The homogenization also can beperformed in a chamber with supercritical fluids, such as carbon dioxideor the like.

In another embodiment, the DCM process is conducted with a metal piecethat becomes an integral part of the consolidated polymeric article. Forexample, a combination of antioxidant/anti-crosslinking agent-containingpolyethylene resin, powder, or flake and anantioxidant/anti-crosslinking agent-poor polyethylene resin, powder, orflake is direct compression molded into a metallic acetabular cup or atibial base plate. The porous tibial metal base plate is placed in themold, antioxidant/anti-crosslinking agent-rich polymeric resin, powder,or flake is added on top and then antioxidant/anti-crosslinkingagent-poor polymeric resin, powder, or flake is added last, for example.After consolidation and irradiation, doping of the article with at leastone antioxidant is optionally carried out to further stabilize the freeradicals. Prior to the DCM consolidation, the pores of the metal piececan be filled with a waxy or plaster substance through half thethickness to achieve polyethylene interlocking through the otherunfilled half of the metallic piece. The pore filler is maintainedthrough the irradiation and subsequent antioxidant doping steps toprevent infusion of antioxidant in to the pores of the metal. In someembodiments, the article is machined after doping to shape an implant.

In another embodiment, there are more than one metal pieces integral tothe polymeric article.

In another embodiment, one or some or all of the metal pieces integralto the polymeric article is a porous metal piece that allows bonein-growth when implanted into the human body.

In some embodiments, one or some or all of the metal pieces integral tothe polymeric article is a non-porous metal piece.

In one embodiment, the consolidated polymeric article is irradiatedusing ionizing radiation such as gamma, electron-beam, or x-ray to adose level between about 1 and about 10,000 kGy, preferably about 25 toabout 250 kGy, preferably about 50 to about 150 kGy, preferably about 65kGy, preferably about 85 kGy, or preferably about 100 kGy, or preferablyabout 150 kGy.

In another embodiment, the irradiated polymeric article is doped with atleast one antioxidant by placing the article in an antioxidant bath atroom temperature or at an elevated temperature for a given amount oftime.

In another embodiment, the doped polymeric article is heated below themelting point of the polymeric article.

In one embodiment, the metal mesh of the implant is sealed using asealant to prevent or reduce the infusion of antioxidant into the poresof the mesh during the selective doping of the implant. Preferably, thesealant is water soluble. But other sealants are also used. The finalcleaning step that the implant is subjected to also removes the sealant.Alternatively, an additional sealant removal step is used. Such sealantsas water, saline, aqueous solutions of water soluble polymers such aspoly-vinyl alcohol, water soluble waxes, plaster of Paris, or others areused. In addition, a photoresist like SU-8, or other, may be curedwithin the pores of the porous metal component. Following processing,the sealant may be removed via an acid etch or a plasma etch.

In another embodiment, the polyethylene-porous metal mono-block is dopedso that the polymeric material is fully immersed in antioxidant orantioxidant solution but the porous metal is either completely above theantioxidant solution surface or only partially immersed during doping.This reduces infusion of antioxidant into the pores of the metal mesh.

In yet another embodiment, the doped polymeric article is machined toform a medical implant. In some embodiments, the machining is carriedout on sides with no metallic piece if at least one is present.

In many embodiments, the medical devices are packaged and sterilized.

In another aspect of the invention, the medical device is cleaned beforepackaging and sterilization.

In other embodiments, the antioxidant/anti-crosslinking agent, such asvitamin E, concentration profiles in device/implant components can becontrolled in several different ways, following various processing stepsand in different orders, for example:

-   -   I. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        machining of implants, radiation cross-linking (at a temperature        below the melting point of the polymeric material), and doping        with at least one antioxidant;    -   II. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        machining of implants, radiation cross-linking (at a temperature        below the melting point of the polymeric material), doping with        at least one antioxidant and homogenizing;    -   III. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        machining of implants, radiation cross-linking (at a temperature        below the melting point of the polymeric material), doping with        at least one antioxidant and homogenizing, extracting/eluting        out the excess antioxidant or at least a portion of the        antioxidant;    -   IV. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        machining of preforms, radiation cross-linking (at a temperature        below the melting point of the polymeric material), doping with        at least one antioxidant, machining of devices and implants;    -   V. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        machining of preforms, radiation cross-linking (at a temperature        below the melting point of the polymeric material), doping with        at least one antioxidant and homogenizing, machining of devices        and implants;    -   VI. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        machining of preforms, radiation cross-linking (at a temperature        below the melting point of the polymeric material), doping with        at least one antioxidant and homogenizing, machining of        implants, extraction of antioxidant;    -   VII. Radiation cross-linking of consolidated polymeric material        (at a temperature below the melting point of the polymeric        material), machining implant, doping with at least one        antioxidant, extracting/eluting out the excess antioxidant or at        least a portion of the antioxidant;    -   VIII. Radiation cross-linking of consolidated polymeric material        (at a temperature below the melting point of the polymeric        material), machining implants, doping with at least one        antioxidant and homogenizing, extracting/eluting out the excess        antioxidant or at least a portion of the antioxidant;    -   IX. Radiation cross-linking of consolidated polymeric material        (at a temperature below the melting point of the polymeric        material), machining prefoms, doping with at least one        antioxidant, extraction of the antioxidant, machining of devices        and implants;    -   X. Radiation cross-linking of consolidated polymeric material        (at a temperature below the melting point of the polymeric        material), machining prefoms, doping with at least one        antioxidant and homogenizing, extracting/eluting out the excess        antioxidant or at least a portion of the antioxidant, machining        of devices and implants;    -   XI. Radiation cross-linking of consolidated polymeric material        (at a temperature below the melting point of the polymeric        material), machining prefoms, doping with at least one        antioxidant, machining of implants, extracting/eluting out the        excess antioxidant or at least a portion of the antioxidant;        and/or    -   XII. Radiation cross-linking of consolidated polymeric material        (at a temperature below the melting point of the polymeric        material), machining prefoms, doping with at least one        antioxidant and homogenizing, machining of implants,        homogenizing, extracting/eluting out the excess antioxidant or        at least a portion of the antioxidant;    -   XIII. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        radiation cross-linking, and machining of devices and implants;    -   XIV. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        radiation cross-linking, machining of implants and doping with        at least one antioxidant;    -   XV. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        radiation cross-linking, doping with at least one antioxidant        and machining of devices and implants;    -   XVI. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        radiation cross-linking, machining of devices and implants,        doping with at least one antioxidant and homogenizing;    -   XVII. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        radiation cross-linking, doping with at least one antioxidant,        homogenizing and machining of devices and implants;    -   XVIII. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        partially extracting/eluting out antioxidant/anti-crosslinking        agent; radiation cross-linking;    -   XIX. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        machining of implants, partially extracting/eluting out anti        oxidant/anti-crosslinking agent; radiation cross-linking;    -   XX. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        partially extracting/eluting out antioxidant/anti-crosslinking        agent; machining of devices and implants and radiation        cross-linking;    -   XXI. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        partially extracting/eluting out antioxidant/anti-crosslinking        agent; machining of implants, radiation cross-linking, doping        with at least one antioxidant;    -   XXII. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        partially extracting/eluting out antioxidant/anti-crosslinking        agent; machining of devices and implants, radiation        cross-linking, homogenizing;    -   XXIII. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend,        partially extracting/eluting out antioxidant/anti-crosslinking        agent; machining of devices and implants, radiation        cross-linking, doping with at least one antioxidant and        homogenizing;    -   XXIV. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend        directly as devices and implants, and radiation cross-linking;    -   XXV. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend        directly as devices and implants, partially extracting/eluting        out antioxidant/anti-crosslinking agent and radiation        cross-linking;    -   XXVI. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend        directly as devices and implants, radiation cross-linking and        homogenizing;    -   XXVII. Blending the antioxidant/anti-crosslinking agent and        polyethylene resin, powder, or flakes, consolidating the blend        directly as devices and implants, partially extracting/eluting        out antioxidant/anti-crosslinking agent, radiation cross-linking        and homogenizing.

In another embodiment, all of the above processes are further followedby cleaning, packaging and sterilization (gamma irradiation, e-beamirradiation, ethylene oxide or gas plasma sterilization).

Methods and Sequence of Irradiation:

The selective, controlled manipulation of polymers and polymer alloysusing radiation chemistry can, in another aspect, be achieved by theselection of the method by which the polymer is irradiated. Theparticular method of irradiation employed, either alone or incombination with other aspects of the invention, such as the polymer orpolymer alloy chosen, contribute to the overall properties of theirradiated polymer.

Gamma irradiation or electron radiation may be used. In general, gammairradiation results in a higher radiation penetration depth thanelectron irradiation. Gamma irradiation, however, generally provides lowradiation dose rate and requires a longer duration of time, which canresult in more in-depth and extensive oxidation, particularly if thegamma irradiation is carried out in air. Oxidation can be reduced orprevented by carrying out the gamma irradiation in an inert gas, such asnitrogen, argon, neon, or helium, or under vacuum. Electron irradiation,in general, results in more limited dose penetration depth, but requiresless time and, therefore, reduces the risk of extensive oxidation if theirradiation is carried out in air. In addition if the desired doselevels are high, for instance 20 Mrad, the irradiation with gamma maytake place over one day, leading to impractical production times. On theother hand, the dose rate of the electron beam can be adjusted byvarying the irradiation parameters, such as conveyor speed, scan width,and/or beam power. With the appropriate parameters, a 20 Mradmelt-irradiation can be completed in for instance less than 10 minutes.The penetration of the electron beam depends on the beam energy measuredby million electron-volts (MeV). Most polymers exhibit a density ofabout 1 g/cm³, which leads to the penetration of about 1 cm with a beamenergy of 2-3 MeV and about 4 cm with a beam energy of 10 MeV. Ifelectron irradiation is preferred, the desired depth of penetration canbe adjusted based on the beam energy. Accordingly, gamma irradiation orelectron irradiation may be used based upon the depth of penetrationpreferred, time limitations and tolerable oxidation levels.

According to certain embodiments, the cross-linked polymeric materialcan have a melt history, meaning that the polymeric material is meltedconcurrently with or subsequent to irradiation for cross-linking.According to other embodiments, the cross-linked polymeric material hasno such melt history.

Various irradiation methods including IMS, CIR, CISM (a.k.a. CLR-SM),WIR, and WIAM are defined and described in greater detail below forcross-linked polymeric materials with a melt history, that is irradiatedwith concurrent or subsequent melting:

(i) Irradiation in the Molten State (IMS):

Melt-irradiation (MIR), or irradiation in the molten state (“IMS”), isdescribed in detail in U.S. Pat. No. 5,879,400. In the IMS process, thepolymer to be irradiated is heated to at or above its melting point.Then, the polymer is irradiated. Following irradiation, the polymer iscooled.

Prior to irradiation, the polymer is heated to at or above its meltingtemperature and maintained at this temperature for a time sufficient toallow the polymer chains to achieve an entangled state. A sufficienttime period may range, for example, from about 5 minutes to about 3hours or to about 24 hours.

The temperature of melt-irradiation for a given polymer depends on theDSC (measured at a heating rate of 10° C./min during the first heatingcycle) peak melting temperature (“PMT”) for that polymer. In general,the irradiation temperature in the IMS process is at least about 2° C.higher than the PMT, more preferably between about 2° C. and about 20°C. higher than the PMT, and most preferably between about 5° C. andabout 10° C. higher than the PMT.

Exemplary ranges of acceptable total dosages are disclosed in greaterdetail in U.S. Pat. Nos. 5,879,400, and 6,641,617, and InternationalApplication WO 97/29793. For example, preferably a total dose of aboutor greater than 1 MRad is used. More preferably, a total dose of greaterthan about 10 Mrad is used.

In electron beam IMS, some energy deposited by the electrons isconverted to heat. This primarily depends on how well the sample isthermally insulated during the irradiation. With good thermalinsulation, most of the heat generated is not lost to the surroundingsand leads to the radiation generated heating (including adiabatic andpartially adiabatic) of the polymer to a higher temperature than theirradiation temperature. The heating could also be induced by using ahigh enough dose rate to minimize the heat loss to the surroundings. Insome circumstance, heating may be detrimental to the sample that isbeing irradiated. Gaseous by-products, such as hydrogen gas when thepolymer is irradiated, are formed during the irradiation. Duringirradiation, if the heating is rapid and high enough to cause rapidexpansion of the gaseous by-products, and thereby not allowing them todiffuse out of the polymer, the polymer may cavitate. The cavitation isnot desirable in that it leads to the formation of defects (such as airpockets, cracks) in the structure that could in turn adversely affectthe mechanical properties of the polymer and in vivo performance of thedevice made thereof.

The temperature rise depends on the dose level, level of insulation,and/or dose rate. The dose level used in the irradiation stage isdetermined based on the desired properties. In general, the thermalinsulation is used to avoid cooling of the polymer and maintaining thetemperature of the polymer at the desired irradiation temperature.Therefore, the temperature rise can be controlled by determining anupper dose rate for the irradiation.

In embodiments of the present invention in which electron radiation isutilized, the energy of the electrons can be varied to alter the depthof penetration of the electrons, thereby controlling the degree ofcross-linking following irradiation. The range of suitable electronenergies is disclosed in greater detail in U.S. Pat. Nos. 5,879,400,6,641,617, and International Application WO 97/29793. In one embodiment,the energy is about 0.5 MeV to about 12 MeV. In another embodiment theenergy is about 1 MeV to 10 MeV. In another embodiment, the energy isabout 10 MeV.

(ii) Cold Irradiation (CIR):

Cold irradiation is described in detail in U.S. Pat. No. 6,641,617, U.S.Pat. No. 6,852,772, and WO 97/29793. In the cold irradiation process, apolymer is provided at room temperature or below room temperature.Preferably, the temperature of the polymer is about 20° C. Then, thepolymer is irradiated. In one embodiment of cold irradiation, thepolymer may be irradiated at a high enough total dose and/or at a fastenough dose rate to generate enough heat in the polymer to result in atleast a partial melting of the crystals of the polymer.

Gamma irradiation or electron radiation may be used. In general, gammairradiation results in a higher dose penetration depth than electronirradiation. Gamma irradiation, however, generally requires a longerduration of time, which can result in more in-depth oxidation,particularly if the gamma irradiation is carried out in air. Oxidationcan be reduced or prevented by carrying out the gamma irradiation in aninert gas, such as nitrogen, argon, neon, or helium, or under vacuum.Electron irradiation, in general, results in more limited dosepenetration depths, but requires less time and, therefore, reduces therisk of extensive oxidation. Accordingly, gamma irradiation or electronirradiation may be used based upon the depth of penetration preferred,time limitations and tolerable oxidation levels.

The total dose of irradiation may be selected as a parameter incontrolling the properties of the irradiated polymer. In particular, thedose of irradiation can be varied to control the degree of cross-linkingin the irradiated polymer. The preferred dose level depends on themolecular weight of the polymer and the desired properties that can beachieved following irradiation. In general, increasing the dose levelwith OR leads to an increase in wear resistance.

Exemplary ranges of acceptable total dosages are disclosed in greaterdetail in U.S. Pat. Nos. 6,641,617 and 6,852,772, InternationalApplication WO 97/29793, and in the embodiments below. In oneembodiment, the total dose is about 0.5 MRad to about 1,000 Mrad. Inanother embodiment, the total dose is about 1 MRad to about 100 MRad. Inyet another embodiment, the total dose is about 4 MRad to about 30 MRad.In still other embodiments, the total dose is about 20 MRad or about 15MRad.

If electron radiation is utilized, the energy of the electrons also is aparameter that can be varied to tailor the properties of the irradiatedpolymer. In particular, differing electron energies results in differentdepths of penetration of the electrons into the polymer. The practicalelectron energies range from about 0.1 MeV to 16 MeV giving approximateiso-dose penetration levels of 0.5 mm to 8 cm, respectively. A preferredelectron energy for maximum penetration is about 10 MeV, which iscommercially available through vendors such as Studer (Daniken,Switzerland) or E-Beam Services (New Jersey, USA). The lower electronenergies may be preferred for embodiments where a surface layer of thepolymer is preferentially cross-linked with gradient in cross-linkdensity as a function of distance away from the surface.

(iii) Warm Irradiation (WIR):

Warm irradiation is described in detail in U.S. Pat. No. 6,641,617 andWO 97/29793. In the warm irradiation process, a polymer is provided at atemperature above room temperature and below the melting temperature ofthe polymer. Then, the polymer is irradiated. In one embodiment of warmirradiation, it has been termed “warm irradiation adiabatic melting” or“WIAM.” In a theoretical sense, adiabatic means an absence of heattransfer to the surroundings. In a practical sense, which applies here,such heating can be achieved by the combination of insulation,irradiation dose rates and irradiation time periods, as disclosed hereinand in the documents cited herein. However, there are situations whereirradiation causes heating, but there is still a loss of energy to thesurroundings. Also, not all warm irradiation refers to an adiabatic.Warm irradiation also can have non-adiabatic or partially (such as about10-75% of the heat generated is lost to the surroundings) adiabaticheating. In all embodiments of WIR, the polymer may be irradiated at ahigh enough total dose and/or a high enough dose rate to generate enoughheat in the polymer to result in at least a partial melting of thecrystals of the polymer, meaning some but not all molecules transitionfrom the crystalline to the amorphous state.

The polymer may be provided at any temperature below its melting pointbut preferably above room temperature. The temperature selection dependson the specific heat and the enthalpy of melting of the polymer and thetotal dose level used. The equation provided in U.S. Pat. No. 6,641,617and International Application WO 97/29793 may be used to calculate thepreferred temperature range with the criterion that the finaltemperature of polymer maybe below or above the melting point.Preheating of the polymer to the desired temperature may be done in aninert (such as under nitrogen, argon, neon, or helium, or the like, or acombination thereof) or non-inert environment (such as air).

In general terms, the pre-irradiation heating temperature of the polymercan be adjusted based on the peak melting temperature (PMT) measure onthe DSC at a heating rate of 10° C./min during the first heat. In oneembodiment the polymer is heated to about 20° C. to about PMT. Inanother embodiment, the polymer is pre-heated to about 90° C. In anotherembodiment, the polymer is heated to about 100° C. In anotherembodiment, the polymer is pre-heated to about 30° C. below PMT and 2°C. below PMT. In another embodiment, the polymer is pre-heated to about12° C. below PMT. The polymer can be pre-heated to up to 300° C. beforeirradiation and cooled down to initial irradiation temperature.

In the WIAM embodiment of WIR, the temperature of the polymer followingirradiation is at or above the melting temperature of the polymer.Exemplary ranges of acceptable temperatures following irradiation aredisclosed in greater detail in U.S. Pat. No. 6,641,617 and InternationalApplication WO 97/29793. In one embodiment, the temperature followingirradiation is about room temperature to PMT, or about 40° C. to PMT, orabout 100° C. to PMT, or about 110° C. to PMT, or about 120° C. to PMT,or about PMT to about 200° C. These temperature ranges depend on thepolymer's PMT and is much higher with reduced level of hydration. Inanother embodiment, the temperature following irradiation is about 145°C. to about 190° C. In yet another embodiment, the temperature followingirradiation is about 145° C. to about 190° C. In still anotherembodiment, the temperature following irradiation is about 150° C.

In WIR, gamma irradiation or electron radiation may be used. In general,gamma irradiation results in a higher dose penetration depth thanelectron irradiation. Gamma irradiation, however, generally requires alonger duration of time, which can result in more in-depth oxidation,particularly if the gamma irradiation is carried out in air. Oxidationcan be reduced or prevented by carrying out the gamma irradiation in aninert gas, such as nitrogen, argon, neon, or helium, or under vacuum.Electron irradiation, in general, results in more limited dosepenetration depths, but requires less time and, therefore, reduces therisk of extensive oxidation. Accordingly, gamma irradiation or electronirradiation may be used based upon the depth of penetration preferred,time limitations and tolerable oxidation levels. In the WIAM embodimentof WIR, electron radiation is used.

The total dose of irradiation may also be selected as a parameter incontrolling the properties of the irradiated polymer. In particular, thedose of irradiation can be varied to control the degree of cross-linkingin the irradiated polymer. Exemplary ranges of acceptable total dosagesare disclosed in greater detail in U.S. Pat. No. 6,641,617 andInternational Application WO 97/29793.

The dose rate of irradiation also may be varied to achieve a desiredresult. The dose rate is a prominent variable in the WIAM process. Thepreferred dose rate of irradiation would be to administer the totaldesired dose level in one pass under the electron-beam. One also candeliver the total dose level with multiple passes under the beam,delivering a (equal or unequal) portion of the total dose at each time.This would lead to a lower effective dose rate.

Ranges of acceptable dose rates are exemplified in greater detail inU.S. Pat. No. 6,641,617 and International Application WO 97/29793. Ingeneral, the dose rates vary between 0.5 Mrad/pass and 50 Mrad/pass. Theupper limit of the dose rate depends on the resistance of the polymer tocavitation/cracking induced by the irradiation.

If electron radiation is utilized, the energy of the electrons also is aparameter that can be varied to tailor the properties of the irradiatedpolymer. In particular, differing electron energies result in differentdepths of penetration of the electrons into the polymer. The practicalelectron energies range from about 0.1 MeV to 16 MeV giving approximateiso-dose penetration levels of 0.5 mm to 8 cm, respectively. Thepreferred electron energy for maximum penetration is about 10 MeV, whichis commercially available through vendors such as Studer (Daniken,Switzerland) or E-Beam Services New Jersey, USA). The lower electronenergies may be preferred for embodiments where a surface layer of thepolymer is preferentially cross-linked with gradient in cross-linkdensity as a function of distance away from the surface.

(iv) Subsequent Heating—Substantial Reduction of Detectable ResidualFree Radicals:

Depending on the polymer or polymer alloy used, and whether the polymerwas irradiated below its melting point, there may be residual freeradicals left in the material following the irradiation process. Apolymer irradiated below its melting point with ionizing radiationcontains cross-links as well as long-lived trapped free radicals. Someof the free radicals generated during irradiation become trapped in thecrystalline regions and/or at crystalline lamellae surfaces leading tooxidation-induced instabilities in the long-term (see Kashiwabara, H. S.Shimada, and Y. Hori, Radiat. Phys. Chem., 1991, 37(1): p. 43-46; Jahan,M. S. and C. Wang, Journal of Biomedical Materials Research, 1991, 25:p. 1005-1017; Sutula, L. C., et al., Clinical Orthopedic RelatedResearch, 1995, 3129: p. 1681-1689.). The elimination of these residual,trapped free radicals through heating can be, therefore, desirable inprecluding long-term oxidative instability of the polymer. Jahan M. S.and C. Wang, Journal of Biomedical Materials Research, 1991, 25: p.1005-1017; Sutula, L. C., et al., Clinical Orthopedic Related Research,1995, 319: p. 28-4. For polymer blends with antioxidants, it may also bedesirable to reduce residual free radicals to preserve the efficiencyand activity of the antioxidant(s).

Residual free radicals may be reduced by heating the polymer above themelting point of the polymer used. The heating allows the residual freeradicals to recombine with each other. If for a given system the preformdoes not have substantially any detectable residual free radicalsfollowing irradiation, then a later heating step may be omitted. Also,if for a given system the concentration of the residual free radicals islow enough to not lead to degradation of device performance, the heatingstep may be omitted.

The reduction of free radicals to the point where there aresubstantially no detectable free radicals can be achieved by heating thepolymer to above the melting point. The heating provides the moleculeswith sufficient mobility so as to eliminate the constraints derived fromthe crystals of the polymer, thereby allowing essentially all of theresidual free radicals to recombine. Preferably, the polymer is heatedto a temperature between the peak melting temperature (PMT) anddegradation temperature (T_(d)) of the polymer, more preferably betweenabout 3° C. above PMT and T_(d), more preferably between about 10° C.above PMT and 340° C., more preferably between about 10° C. and 12° C.above PMT and most preferably about 15° C. above PMT. The elongation ofthe polymeric materials may be increased when heated to about 300° C.

In certain embodiments, there may be an acceptable level of residualfree radicals in which case, the post-irradiation annealing also can becarried out below the melting point of the polymer, the effects of suchfree radicals can be minimized or eliminated by an antioxidant.

(v) Sequential Irradiation:

The polymer is irradiated with either gamma or e-beam radiation in asequential manner. With e-beam the irradiation is carried out withmultiple passes under the beam and with gamma radiation the irradiationis carried out in multiple passes through the gamma source. Optionally,the polymer is thermally treated in between each or some of theirradiation passes. The thermal treatment can be heating below themelting point or at the melting, point of the polymer. The irradiationat any of the steps can be warm irradiation, cold irradiation, or meltirradiation, or any combination thereof. For example the polymer isirradiated with 30 kGy at each step of the cross-linking and it is firstheated to about 120° C. and then annealed at about 120° C. for about 5hours after each irradiation cycle.

(vi) Blending and Doping:

As stated above, the cross-linked polymeric material can optionally havea melt history, meaning it is melted before, concurrent with orsubsequent to irradiation. The polymeric material can be blended with anantioxidant prior to consolidation and irradiation. Also, theconsolidated polymeric material can be doped with an antioxidant priorto or after irradiation, and optionally can have been melted before,concurrent with or subsequent to irradiation. Furthermore, a polymericmaterial can both be blended with an antioxidant prior to consolidationand doped with an antioxidant after consolidation (before or afterirradiation and optional melting). The polymeric material can besubjected to extraction at different times during the process, and canbe extracted multiple times as well.

The polymeric material can be blended with any of the antioxidants,including alpha-ocopherol (such as vitamin E), delta-tocopherol; propyl,octyl, or dedocyl gallates; lactic, citric, ascorbic, tartaric acids,and organic acids, and their salts; orthophosphates; tocopherol acetate;lycopene; or a combination thereof. Other possible antioxidants aregiven under the definition of ‘antioxidant’.

High temperature melting of UHMWPE can serve several different purposes.One is the transformation of the crystalline regions to amorphous suchthat when an irradiated material is recrystallized, the residual freeradicals in the crystalline regions have been eliminated. Anotherpurpose is the increase in chain entanglement, increasing the ductilityof the melted material. A third is the creation of increased chain ends(as observed by increased vinyl index), creating cross-linkable moietiesin the material. Interestingly, when a high temperature melted UHMWPE issubsequently irradiated, the cross-link density is decreased compared toa non-high temperature inched and irradiated UHMWPE but the wear rate islower. Unlike melting below 200° C., where the duration of melting haslittle or no effect on mechanical or subsequent radiation cross-linkingproperties, high temperature melting above 200° C. results in strongtime- and temperature-dependence of the resultant properties. Inaddition, the cross-link density of the prior or subsequently irradiatedUHMWPE is dependent on the temperature and duration of the hightemperature melting. Since high temperature melting can change themorphology of the polymer and the distribution of entanglements andcross-links, high temperature melting after high pressurecrystallization can also result in a different material than meltingbelow 200° C.

The resulting properties of high temperature melted UHMWPE is alsodependent on the environment of the melting process, i.e. contact withair when the material is above 200° C. changes the propertiesdramatically. The inclusion of an antioxidant is preferred during hightemperature melting and can hinder some of the effects of air exposureon the mechanical and wear properties.

In addition, the effect of a free radical scavenger/antioxidant togetherwith high temperature melting has various effects on prior orsubsequently irradiated UHMWPE. For example, vitamin E hinders radiationcross-linking as a function of concentration when present in UHMWPEduring irradiation, and the wear rate of this UHMWPE is increased whencompared to UHMWPE irradiated without vitamin E. In contrast, hightemperature melting decreases the wear rate of irradiated UHMWPE despitea decrease in cross-link density. Therefore, combinations of vitamin Eand high temperature melting processes before and after radiationcross-linking can be optimized to result in a variety of materials withlow wear and high ductility. Also, spatial control of a non-uniformvitamin E concentration or a non-uniform high temperature meltingprofile can result in a material with non-uniform cross-linking,ductility, wear resistance and toughness and can be tailored accordingto the application.

DEFINITIONS AND OTHER EMBODIMENTS

The term “toughness” of a material refers to its ability to distributean applied stress such that failure does not occur until there are veryhigh stresses. It is quantified by the area under the stress-straincurve of a material. For example, a higher work-to-failure, which is thearea under the engineering stress-strain curve obtained from tensilemechanical testing is attributed directly to increased toughness. Forexample, toughness also refers to impact toughness, which is thework-to-failure as measured by impact testing. In the examples, this isdemonstrated by IZOD impact testing according to ASTM F648.

“Ductility” refers to the ability of a material to plastically deformunder stress. Ductility can be quantified as the total energy absorbedby plastic deformation; i.e. the area under the curve of the plasticsegment of the engineering stress-strain curve. In the examples,increased elongation to break is attributed to increased ductility sincethe yield strength of these materials are relatively similar.

“Antioxidant” refers to what is known in the art as (see, for example,WO 01/80778, U.S. Pat. No. 6,448,315). Alpha- and delta-tocopherol;propyl, octyl, or dedocyl gallates; lactic, citric, ascorbic, tartaricacids, and organic acids, and their salts; orthophosphates, lycopene,tocopherol acetate are generally known form of antioxidants.Antioxidants are also referred as free radical scavengers, include:glutathione, lipoic acid, vitamins such as ascorbic acid (vitamin C),vitamin B, vitamin D, vitamin-E, tocopherols (synthetic or natural,alpha-, gamma-, delta-), acetate vitamin esters, water solubletocopherol derivatives, tocotrienols, water soluble tocotrienolderivatives; melatonin, carotenoids, including various carotenes,lutein, pycnogenol, glycosides, trehalose, polyphenols and flavonoids,quercetin, lycopene, lutein, selenium, nitric oxide, curcuminoids,2-hydroxytetronic acid; cannabinoids, synthetic antioxidants such astertiary butyl hydroquinone, 6-amino-3-pyrodinoles, butylatedhydroxyanisol e, butylated hydroxytoluene, ethoxyquin, tannins, propylgallate, other gallates, Aquanox family; Irganox® and Irganox® Bfamilies including Irganox® 1010, Irganox® 1076, Irganox® 1330; Irgafos®family including Irgafos® 168; phenolic compounds with different chainlengths, and different number of OH groups; enzymes with antioxidantproperties such as superoxide dismutase, herbal or plant extracts withantioxidant properties such as St. John's Wort, green tea extract, grapeseed extract, rosemary, oregano extract, mixtures, derivatives,analogues or conjugated forms of these. Antioxidants/free radicalscavengers can be primary antioxidants with reactive OH or NH groupssuch as hindered phenols or secondary aromatic amines, they can besecondary antioxidants such as organophosphorus compounds orthiosynergists, they can be multifunctional antioxidants,hydroxylamines, or carbon centered radical scavengers such as lactonesor acrylated bis-phenols. The antioxidants can be selected individuallyor used in any combination.

Irganox®, as described herein refers to a family of antioxidantsmanufactured by Ciba Specialty Chemicals. Different antioxidants aregiven numbers following the Irganox® name, such as Irganox® 1010,Irganox® 1035, Irganox® 1076, Irganox® 1098, etc. Irgafos® refers to afamily of processing stabilizers manufactured by Ciba SpecialtyChemicals. Irganox® family has been expanded to include blends ofdifferent antioxidants with each other and with stabilizers fromdifferent families such as the Irgafos family. These have been givendifferent initials after the Irganox® name, for instance, the Irganox®HP family are synergistic combinations of phenolic antioxidants,secondary phosphate stabilizers and the lactone Irganox® HP-136.Similarly, there are Irganox® B (blends), Irganox® L (aminic), Irganox®E (with vitamin E), Irganox® ML, Irganox® MD families. Herein we discussthese antioxidants and stabilizers by their tradenames, but otherchemicals with equivalent chemical structure and activity can be used.Addition, these chemicals can be used individually or in mixtures of antcomposition. Some of the chemical structures and chemical names of theantioxidants in the Irganox® family are listed in Table 23.

“Anti-crosslinking agent” is a chemical compound which reduces theresultant cross-link density as a result of crosslinking processes inthe polymer such as ionizing radiation exposure when it is blended withthe polymer. Anti-crosslinking agents can be antioxidants as well. Theycan act when they are present in the polymer at any concentration orthey may be activated when they are present at a threshold concentrationor they may act only when activated by an additional additive.

“Supercritical fluid” refers to what is known in the art, for example,supercritical propane, acetylene, carbon dioxide (CO₂). In thisconnection the critical temperature is that temperature above which agas cannot be liquefied by pressure alone. The pressure under which asubstance may exist as a gas in equilibrium with the liquid at thecritical temperature is the critical pressure. Supercritical fluidcondition generally means that the fluid is subjected to such atemperature and such a pressure that a supercritical fluid and thereby asupercritical fluid mixture is obtained, the temperature being above thesupercritical temperature, which for CO₂ is 31.3° C., and the pressurebeing above the supercritical pressure, which for CO₂ is 73.8 bar. Morespecifically, supercritical condition refers to a condition of amixture, for example, UHMWPE with an antioxidant, at an elevatedtemperature and pressure, when a supercritical fluid mixture is formed;and then evaporate CO₂ from the mixture, UHMWPE doped with anantioxidant is obtained (see, for example, U.S. Pat. No. 6,448,315 andWO 02/26464). Other supercritical fluids can be chosen from the group ofwater, chloroform, nitric oxide, elementary gasses such as argon,nitrogen, organic acomounds such as acetic acid, benzene, ethanol,ethylene oxide, methanol, methyl ethyl ketone, monolefins such asethylene, propylene, or paraffins such as ethane, methane, propane,n-butane, n-heptane. A co-solvent or a mixture of fluids can be used.

The term “compression molding” as referred herein related generally towhat is known in the art and specifically relates to high temperaturemolding polymeric material wherein polymeric material is in any physicalstate, including resin, powder, or flake form, is compressed into a slabform or mold of a medical implant, for example, a tibial insert, anacetabular liner, a glenoid liner, a patella, or an unicompartmentalinsert, an interpositional device for any joint can be machined.

The term “layered molding” refers to consolidating a polymeric materialby compression molding one or more of its resin forms, which may be inthe form of flakes, powder, pellets or the like or consolidated forms inlayers such that there are distinct regions in the consolidated formcontaining different concentrations of constituents. These resin formsinclude blends of the polymeric material with other polymers in theirresin forms and other chemicals such as antioxidants. The antioxidantscould be blended with the polymeric material in solid, liquid, orsolution form. Examples of such layered molded polymeric material areshown in FIGS. 42a, 46a-g, 47a-c, 68a-e and 69.

Whenever a layered-molded UHMWPE is described in the examples below andis used in any of the embodiments it can be fabricated by:

-   -   1. layered molding of UHMPWE resin powder or its        antioxidant/anti-crosslinking agent blends where        -   a. one or more layers contain no antioxidant or            anti-crosslinking agent and one or more layers contain one            or more additives, antioxidants and/or anti-crosslinking            agents, or        -   b. one or more layers contain one or more antioxidants            and/or anti-crosslinking agents and one or more layers            contain one or more antioxidants and/or anti-crosslinking            agents where in the concentration of at least one            antioxidant/anti-crosslinking agent is higher in one layer            than another, or        -   c. at least one layer contains an antioxidant from the            Irganox® family and another contains vitamin E, or        -   d. at least one layer contains Irganox® 1010 and another            contains vitamin E, or        -   e. at least one layer contains Irganox® 1010 and a second            contains Irganox® 1010 at a higher concentration;    -   2. molding together of previously molded layers of UHMWPE        containing different or identical concentration of        antioxidants/anti-crosslinking agents where        -   a. one or more layers contain no antioxidant or            anti-crosslinking agent and one or more layers contain one            or more additives, antioxidants and/or anti-crosslinking            agents, or        -   b. one or more layers contain one or more antioxidants            and/or anti-crosslinking agents and one or more layers            contain one or more antioxidants and/or anti-crosslinking            agents where in the concentration of at least one            antioxidant/anti-crosslinking agent is higher in one layer            than another, or        -   c. at least one layer contains an antioxidant from the            Irganox® family and another contains vitamin E, or        -   d. at least one layer contains Irganox® 1010 and another            contains vitamin E, or        -   e. at least one layer contains Irganox® 1010 and a second            contains Irganox® 1010 at a higher concentration; and/or    -   3. molding of UHMWPE resin powder with or without        antioxidant/anti-crosslinking agent on to a at least one        previously molded UHMWPE with or without        antioxidant/anti-crosslinking agent where        -   a. one or more layers contain no antioxidant or            anti-crosslinking agent and one or more layers contain one            or more additives, antioxidants and/or anti-crosslinking            agents, or        -   b. one or more layers contain one or more antioxidants            and/or anti-crosslinking agents and one or more layers            contain one or more antioxidants and/or anti-crosslinking            agents where in the concentration of at least one            antioxidant/anti-crosslinking agent is higher in one layer            than another, or        -   c. at least one layer contains an antioxidant from the            Irganox® family and another contains vitamin E, or        -   d. at least one layer contains Irganox® 1010 and another            contains vitamin E, or        -   e. at least one layer contains Irganox® 1010 and a second            contains Irganox® 1010 at a higher concentration.

Layered molding can be done using parallel plates or any plate/moldgeometry which directly result in an implant or implant preform, i.e.direct compression molding. It can also be done such that the polymericmaterial is directly layered compression molded onto a second surface,for example a porous metal to result in an implant or implant preform.An implant preform is a material, which after slight modification suchas machining results in an implant. Preforms are generally oversizedversions of implants, where machining from the surfaces gives the finalimplant surfaces.

The molding process generally involves

(i) heating the layers to be molded,

(ii) pressurizing them together while heated,

(iii) keeping at temperature and pressure, and

(iv) cooling down and releasing pressure.

The order of cooling and pressure release can be used interchangeably.In some embodiments the cooling and pressure release my follow varyingrates independent form each other.

The layers to be molded can be heated in water, air, inert gas or anyenvironment containing a mixture of gases or supercritical fluids beforepressurization. The layers can be pressurized individually at roomtemperature or at an elevated temperature below the melting point orabove the melting point before being molded together: The temperature atwhich the layers are pre-heated can be the same or different from themolding temperature. The temperature can be gradually increased frompre-heat to mold temperature with or without pressure. The pressure towhich the layers are exposed before molding can be gradually increasedor increased and maintained at the same level.

During molding, different regions of the mold can be heated to differenttemperatures. The temperature and pressure can be maintained duringmolding for 1 second up to 1000 hours or longer. During cool-down underpressure, the pressure can be maintained at the molding pressure orincreased or decreased. The cooling rate can be 0.0001° C./minute to120° C./minute or higher. The cooling rate can be different fordifferent regions of the mold. After cooling down to about roomtemperature, the mold can be kept under pressure for 1 second to 1000hours. Or the pressure can be released partially or completely at anelevated temperature.

The term “direct compression molding” (DCM) as referred herein relatedgenerally to what is known in the art and specifically relates tomolding applicable in polyethylene-based devices, for example, medicalimplants wherein polyethylene in any physical state, including resin,powder, or flake form, is compressed to solid support, for example, ametallic back, metallic mesh, or metal surface containing grooves,undercuts, or cutouts. The compression molding also includes hightemperature compression molding of polyethylene at various states,including resin, powder, flakes and particles, to make a component of amedical implant, for example, a tibial insert, an acetabular liner, aglenoid liner, a patella, an interpositional device for any joint or anunicompartmental insert.

The term “Mechanical deformation” refers to a deformation taking placebelow the inciting point of the material, essentially ‘cold-working’ thematerial. The deformation modes include uniaxial, channel flow, uniaxialcompression, biaxial compression, oscillatory compression, tension,uniaxial tension, biaxial tension, ultra-sonic oscillation, bending,plane stress compression (channel die), torsion or a combination of anyof the above. The deformation could be static or dynamic. The dynamicdeformation can be a combination of the deformation modes in small orlarge amplitude oscillatory fashion. Ultrasonic frequencies can be used.All deformations can be performed in the presence of sensitizing gasesand/or at elevated temperatures.

The term “deformed state” refers to a state of the polymeric materialfollowing a deformation process, such as a mechanical deformation, asdescribed herein, at solid or at melt. Following the deformationprocess, deformed polymeric material at a solid state or at melt is beallowed to solidify/crystallize while still maintains the deformed shapeor the newly acquired deformed state.

“IBMA” refers to irradiation below the melt and mechanical annealing.“IBMA” was formerly referred to as “CIMA” (Cold Irradiation andMechanically Annealed).

The term “mechanically interlocked” refers generally to interlocking ofpolymeric material and the counterface, that are produced by variousmethods, including compression molding, heat and irradiation, therebyforming an interlocking interface, resulting into a ‘shape memory’ ofthe interlocked polymeric material. Components of a device having suchan interlocking interface can be referred to as a “hybrid material”.Medical implants having such a hybrid material contain a substantiallysterile interface.

The term “substantially sterile” refers to a condition of an object, forexample, an interface or a hybrid material or a medical implantcontaining interface(s), wherein the interface is sufficiently sterileto be medically acceptable, i.e., will not cause an infection or requirerevision surgery.

“Metallic mesh” refers to a porous metallic surface of various poresizes, for example, 0.1-3 mm. The porous surface can be obtained throughseveral different methods, for example, sintering of metallic powderwith a binder that is subsequently removed to leave behind a poroussurface; sintering of short metallic fibers of diameter 0.1-3 mm; orsintering of different size metallic meshes on top of each other toprovide an open continuous pore structure.

“Bone cement” refers to what is known in the art as an adhesive used inbonding medical devices to bone. Typically, bone cement is made out ofpolymethylmethacrylate (PMMA). Bone cement can also be made out ofcalcium phosphate.

“High temperature compression molding” refers to the compression moldingof polymeric material in any form, for example, resin, powder, flakes orparticles, to impart new geometry under pressure and temperature. Duringthe high temperature (above the melting point of polymeric material)compression molding, polymeric material is heated to above its meltingpoint, pressurized into a mold of desired shape and allowed to cool downunder pressure to maintain a desired shape.

“Shape memory” refers to what is known in the art as the property ofpolymeric material, for example, an UHMWPE, that attains a preferredhigh entropy shape when melted. The preferred high entropy shape isachieved when the resin, powder, or flake is consolidated throughcompression molding.

The phrase “substantially no detectable residual free radicals” refersto a state of a polymeric component, wherein enough free radicals areeliminated to avoid oxidative degradation, which can be evaluated byelectron spin resonance (ESR). The phrase “detectable residual freeradicals” refers to the lowest level of free radicals detectable by ESRor more. The lowest level of free radicals detectable withstate-of-the-art instruments is about 10¹⁴ spins/gram and thus the term“detectable” refers to a detection limit of about 10¹⁴ spins/gram byESR. Thus, the term ‘undetectable’ refers to values below this limit.

The terms “about” or “approximately” in the context of numerical valuesand ranges refers to values or ranges that approximate or are close tothe recited values or ranges such that the invention can perform asintended, such as utilizing a method parameter (e.g., time, dose, doserate/level, and temperature), having a desired degree of cross-linkingand/or a desired lack of or quenching of free radicals, as is apparentto the skilled person from the teachings contained herein. This is due,at least in part, to the varying properties of polymer compositions.Thus, these terms encompass values beyond those resulting fromsystematic error. These terms make explicit what is implicit, as knownto the person skilled in the art.

All ranges set forth herein in the summary and description of theinvention include all numbers or values thereabout or therebetween ofthe numbers of the range. The ranges of the invention expresslydenominate and set forth all integers, decimals and fractional values inthe range. For example, the radiation dose can be about 50 kGy, about 65kGy, about 75 kGy, about 100 kGy, about 200 kGy, about 300 kGy, about400 kGy, about 500 kGy, about 600 kGy, about 700 kGy, about 800 kGy,about 900 kGy, or about 1000 kGy, or above 1000 kGy, or any integer,decimal or fractional value thereabout or therebetween.

“Polymeric materials” or “polymer” include polyethylene, for example,Ultra-high molecular weight polyethylene (UHMWPE) refers to linearnon-branched chains of ethylene having molecular weights in excess ofabout 500,000, preferably above about 1,000,000, and more preferablyabove about 2,000,000. Often the molecular weights can reach about8,000,000 or more. By initial average molecular weight is meant theaverage molecular weight of the UHMWPE starting material, prior to anyirradiation. See U.S. Pat. No. 5,879,400, PCT/US99/16070, filed on Jul.16, 1999, and PCT/US97/02220, filed Feb. 11, 1997, The term“polyethylene article” or “polymeric article” or “polymer” generallyrefers to articles comprising any “polymeric material” disclosed herein.

“Polymeric materials” or “polymer” also include hydrogels, such aspoly(vinyl alcohol), poly(acrylamide), poly(acrylic acid), poly(ethyleneglycol), blends thereof, or interpenetrating networks thereof, which canabsorb water such that water constitutes at least 1 to 10,000% of theiroriginal weight, typically 100 wt % of their original weight or 99% orless of their weight after equilibration in water.

“Polymeric material” or “polymer” can be in the form of resin, flakes,powder, consolidated stock, implant, and can contain additives such asantioxidant(s). The “polymeric material” or “polymer” also can be ablend of one or more of different resin, flakes or powder containingdifferent concentrations of an additive such as an antioxidant. Theblending of resin, flakes or powder can be achieved by the blendingtechniques known in the art. The “polymeric material” also can be aconsolidated stock of these blends.

“Blending” generally refers to mixing of a polyolefin in itspre-consolidated form with an additive. If both constituents are solid,blending can be done dry or by using a third component such as a liquidto mediate the mixing of the two components, after which the liquid isremoved by evaporating (‘solvent blending’). If the additive is liquid,for example α-tocopherol, then the solid can be mixed with largequantities of liquid, then diluted down to desired concentrations withthe solid polymer to obtain uniformity in the blend. In the case wherean additive is also an antioxidant, for example vitamin E, orα-tocopherol, then blended polymeric material is also antioxidant-doped.Polymeric material, as used herein, also applies to blends of apolyolefin and a plasticizing agent, for example a blend of UHMWPE resinpowder blended with α-tocopherol and consolidated. Polymeric material,as used herein, also applies to blends of an additive, a polyolefin anda plasticizing agent, for example UHMWPE soaked in α-tocopherol.

In one embodiment UHMWPE flakes are blended with α-tocopherol;preferably the UHMWPE/α-tocopherol blend is heated to diffuse theα-tocopherol into the flakes. The UHMWPE/α-tocopherol blend is furtherblended with virgin UHMWPE flakes to obtain a blend of UHMWPE flakeswhere some flakes are poor in α-tocopherol and others are rich inα-tocopherol. This blend is then consolidated and irradiated. Duringirradiation the α-tocopherol poor regions are more highly cross-linkedthan the α-tocopherol poor regions. Following irradiation the blend ishomogenized to diffuse α-tocopherol from the α-tocopherol rich toα-tocopherol poor regions and achieve oxidative stability throughout thepolymer.

The products and processes of this invention also apply to various typesof polymeric materials, for example, any polypropylene, any polyimide,any polyether ketone, or any polyolefin, includinghigh-density-polyethylene, low-density-polyethylene,linear-low-density-polyethylene, ultra-high molecular weightpolyethylene (UHMWPE), copolymers or mixtures thereof. The products andprocesses of this invention also apply to various types of hydrogels,for example, poly(vinyl alcohol), poly(ethylene glycol), poly(ethyleneoxide), poly(acrylic acid), poly(methacrylic acid), poly(acrylamide),copolymers or mixtures thereof, or copolymers or mixtures of these withany polyolefin. Polymeric materials, as used herein, also applies topolyethylene of various forms, for example, resin, powder, flakes,particles; powder, or a mixture thereof, or a consolidated form derivedfrom any of the above. Polymeric materials, as used herein, also appliesto hydrogels of various forms, for example, film, extrudate, flakes,particles, powder, or a mixture thereof, or a consolidated form derivedfrom any of the above.

Blending of additives in the polymeric material resin can be done by:

1. Dissolving an antioxidant/anti-crosslinking agent in a solvent or amixture of solvents,

2. Mixing the polymer resin with the antioxidant/anti-crosslinking agentsolution,

3. Drying the solvent by evaporation, optionally using elevatedtemperature or vacuum.

Solvents can be chosen from organic solvents such as acetic acid,acetone, acetonitrile, benzene, butanols, butanone, carbontetrachloride, chlorobenzene, chloroform, cyclohexane,1,2-dicholoethane, diethyl ether, diethylene glycol, diethylene glycoldiethyl ether, 1,2-dimethoxyethane, dimethyl ether, dimethylformamide,dimethyl sulfoxide, dioxane, ethanol, ethyl acetate, ethylene glycol,glycerin, heptane, hexane, methanol, pentane, propanols, pyridine,tetrahydrofuran, toluene, xylene or they can be aqueous solvents.Aqueous solvents can be pure water or solution of other compounds suchas acids, salts, or bases in water. They can be aqueous solutions ofsurfactants (generally amphiphilic compounds) such as fatty acids. Theycan also be inorganic nonaqueous solvents such as liquid alumina.Solvent can also be a supercritical fluid such as supercritical carbondioxide.

The solvent is typically selected depending on the solubility of theantioxidants/anti-crosslinking agents desired to be blended into thepolymer. The polymer resin can optionally dissolve in the same solvent.Different antioxidants/anti-crosslinking agents can be dissolved indifferent solvents and mixed together before mixing in the polymer orcan be separately mixed with the polymer powder. In each case more thanone solvent can be used. Dissolution of theantioxidants/anti-crosslinking agents can be enhanced or enabled byraising the temperature or pressure or raising the temperature andpressure such that the solvent is in the supercritical state.

The term “additive” refers to any material that can be added to a basepolymer in less than 50 v/v %. This material can be organic or inorganicmaterial with a molecular weight less than that of the base polymer. Anadditive can impart different properties to the polymeric material, forexample, it can be a plasticizing agent, a nucleating agent, or anantioxidant.

The term “plasticizing agent” refers to what is known in the art, amaterial with a molecular weight less than that of the base polymer, forexample vitamin E (α-tocopherol) in unirradiated or cross-linkedultrahigh molecular weight polyethylene or low molecular weightpolyethylene in high molecular weight polyethylene, in both casesultrahigh molecular weight polyethylene being the base polymer. Theplasticizing agent is typically added to the base polymer in less thanabout 20 weight percent. The plasticizing agent generally increasesflexibility and softens the polymeric material.

The term “plasticization” or “plasticizing” refers to the propertiesthat a plasticizing agent imparts on the polymeric material to which ithas been contacted with. These properties may include but are notlimited to increased elongation at break, reduced stiffness andincreased ductility.

A “nucleating agent” refers to an additive known in the art, an organicor inorganic material with a molecular weight less than that of the basepolymer, which increases the rate of crystallization in the polymericmaterial. Typically, organocarboxylic acid salts, for example calciumcarbonate, are good nucleation agents for polyolefins. Also, nucleatingagents are typically used in small concentrations such as 0.5 wt %.

“Cross-linking Polymeric Materials” refers to polymeric materials, forexample, UHMWPE can be cross-linked by a variety of approaches,including those employing cross-linking chemicals (such as peroxidesand/or silane) and/or irradiation. Preferred approaches forcross-linking employ irradiation. Cross-linked UHMWPE also can beobtained through cold irradiation, warm irradiation, or melt irradiationaccording to the teachings of U.S. Pat. No. 5,879,400, U.S. Pat. No.6,641,617, and PCT/US97/02220.

“Consolidated polymeric material refers” to a solid, consolidated barstock, solid material machined from stock, or semi-solid form ofpolymeric material derived from any forms as described herein, forexample, resin, powder, flakes, particles, or a mixture thereof, thatcan be consolidated. The consolidated polymeric material also can be inthe form of a slab, block, solid bar stock, machined component, film,tube, balloon, preform, implant, finished medical device or unfinisheddevice.

By “crystallinity” is meant the fraction of the polymer that iscrystalline. The crystallinity is calculated by knowing the weight ofthe sample (weight in grams), the heat absorbed by the sample in melting(E, in J/g) and the heat of melting of polyethylene crystals (ΔH=291J/g), and using the following equation according to ASTM F2625 and thelike or their successors:% Crystallinity=E/w·ΔH

By tensile “elastic modulus” is meant the ratio of the nominal stress tocorresponding strain for strains as determined using the standard testASTM 638 M III and the like or their successors.

The term “non-permanent device” refers to what is known in the art as adevice that is intended for implantation in the body for a period oftime shorter than several months. Some non-permanent devices could be inthe body for a few seconds to several minutes, while other may beimplanted for days, weeks, or up to several months. Non-permanentdevices include catheters, tubing, intravenous tubing, and sutures, forexample.

“Pharmaceutical compound”, as described herein, refers to a drug in theform of a powder, suspension, emulsion, particle, film, cake, or moldedform. The drug can be free-standing or incorporated as a component of amedical device.

The term “packaging” refers to the container or containers in which amedical device is packaged and/or shipped. Packaging can include severallevels of materials, including bags, blister packs, heat-shrinkpackaging, boxes, ampoules, bottles, tubes, trays, or the like or acombination thereof. A single component may be shipped in severalindividual types of package, for example, the component can be placed ina bag, which in turn is placed in a tray, which in turn is placed in abox. The whole assembly can be sterilized and shipped. The packagingmaterials include, but not limited to, vegetable parchments, multi-layerpolyethylene, Nylon 6, polyethylene terephthalate (PET), and polyvinylchloride-vinyl acetate copolymer films, polypropylene, polystyrene, andethylene-vinyl acetate (EVA) copolymers.

The term “interface” in this invention is defined as the niche inmedical devices formed when an implant is in a configuration where acomponent is in contact with another piece (such as a metallic or anon-metallic component), which forms an interface between the polymerand the metal or another polymeric material. For example, interfaces ofpolymer-polymer or polymer-metal are in medical prosthesis, such asorthopedic joints and bone replacement parts, for example, hip, knee,elbow or ankle replacements.

Medical implants containing factory-assembled pieces that are in closecontact with the polyethylene form interfaces. In most cases, theinterfaces are not readily accessible to ethylene oxide gas or the gasplasma during a gas sterilization process.

“Irradiation”, in one aspect of the invention, the type of radiation,preferably ionizing, is used. According to another aspect of theinvention, a dose of ionizing radiation ranging from about 25 kGy toabout 1000 kGy is used. The radiation dose can be about 25 kGy, about 50kGy, about 65 kGy, about 75 kGy, about 100 kGy, about 150, kGy, about200 kGy, about 300 kGy, about 400 kGy, about 500 kGy, about 600 kGy,about 700 kGy, about 800 kGy, about 900 kGy, or about 1000 kGy, or above1000 kGy, or any value thereabout or therebetween. Preferably, theradiation dose can be between about 25 kGy and about 150 kGy or betweenabout 50 kGy and about 100 kGy. These types of radiation, includinggamma, x-ray, and/or electron beam, kills or inactivates bacteria,viruses, or other microbial agents potentially contaminating medicalimplants, including the interfaces, thereby achieving product sterility.The irradiation, which may be electron or gamma irradiation, inaccordance with the present invention can be carried out in airatmosphere containing oxygen, wherein the oxygen concentration in theatmosphere is at least 1%, 2%, 4%, or up to about 22%, or any valuethereabout or therebetween. In another aspect, the irradiation can becarried out in an inert atmosphere, wherein the atmosphere contains gasselected from the group consisting of nitrogen, argon, helium, neon, orthe like, or a combination thereof. The irradiation also can be carriedout in a sensitizing gas such as acetylene or mixture or a sensitizinggas with an inert gas or inert gases. The irradiation also can becarried out in a vacuum. The irradiation can also be carried out at roomtemperature, or at between room temperature and the melting point of thepolymeric material, or at above the melting point of the polymericmaterial. The irradiation can be carried out at any temperature or atany dose rate using e-beam, gamma, and/or x-ray. The irradiationtemperature can be below or above the melting point of the polymer. Thepolymer can be first heated and then irradiated. Alternatively, the heatgenerated by the beam, i.e., radiation generated heating (includingadiabatic and partially adiabatic) can increase the temperature of thepolymer. Subsequent to the irradiation step the polymer can be heated tomelt or heated to a temperature below its melting point for annealing.These post-irradiation thermal treatments can be carried out in air,inert gas and/or in vacuum. Also the irradiation can be carried out insmall increments of radiation dose and in some embodiments thesesequences of incremental irradiation can be interrupted with a thermaltreatment. The sequential irradiation can be carried out with about 1,10, 20, 30, 40, 50, 100 kGy, or higher radiation dose increments.Between each or some of the increments the polymer can be thermallytreated by melting and/or annealing steps. The thermal treatment afterirradiation is mostly to reduce or to eliminate the residual freeradicals in the polymers created by irradiation, and/or eliminate thecrystalline matter, and/or help in the removal of any extractables thatmay be present in the polymer.

In accordance with a preferred feature of this invention, theirradiation may be carried out in a sensitizing atmosphere. This maycomprise a gaseous substance which is of sufficiently small molecularsize to diffuse into the polymer and which, on irradiation, acts as apolyfunctional grafting moiety. Examples include substituted orunsubstituted polyunsaturated hydrocarbons; for example, acetylenichydrocarbons such as acetylene; conjugated or unconjugated olefinichydrocarbons such as butadiene and (meth)acrylate monomers; sulphurmonochloride, with chloro-tri-fluoroethylene (CTFE) or acetylene beingparticularly preferred. By “gaseous” is meant herein that thesensitizing atmosphere is in the gas phase, either above or below itscritical temperature, at the irradiation temperature.

If electron radiation is used, the energy of the electrons also is aparameter that can be varied to tailor the properties of the irradiatedpolymer. In particular, differing electron energies result in differentdepths of penetration of the electrons into the polymer. The practicalelectron energies range from about 0.1 MeV to 16 MeV giving approximateiso-dose penetration levels of 0.5 mm to 8 cm, respectively. Thepreferred electron energy for maximum penetration is about 10 MeV, whichis commercially available through vendors such as Studer (Daniken,Switzerland) or E-Beam Services New Jersey, USA). The lower electronenergies may be preferred for embodiments where a surface layer of thepolymer is preferentially cross-linked with gradient in cross-linkdensity as a function of distance away from the surface.

The term “dose rate” refers to a rate at which the radiation is carriedout. Dose rate can be controlled in a number of ways. One way is bychanging the power of the e-beam, scan width, conveyor speed, and/or thedistance between the sample and the scan horn. Another way is bycarrying out the irradiation in multiple passes with, if desired,cooling or heating steps in-between. With gamma and x-ray radiations thedose rate is controlled by how close the sample is to the radiationsource, how intense is the source, the speed at which the sample passesby the source.

Gamma irradiation, however, generally provides low radiation dose rateand requires a longer duration of time, which can result in morein-depth oxidation, particularly if the gamma irradiation is carried outin air. Electron irradiation, in general, results in a more limited dosepenetration depth, but requires less time and, therefore, reduces therisk of extensive oxidation if the irradiation is carried out in air. Inaddition if the desired dose levels are high, for instance 20 Mrad, theirradiation with gamma may take place over one day, leading toimpractical production times. On the other hand, the dose rate of theelectron beam can be adjusted by varying the irradiation parameters,such as conveyor speed, scan width, and/or beam power. With theappropriate parameters, a 20 Mrad melt-irradiation can be completed infor instance less than 10 minutes. The penetration of the electron beamdepends on the beam energy measured by million electron-volts (MeV).Most polymers exhibit a density of about 1 g/cm³, which leads to thepenetration of about 1 cm with a beam energy of 2-3 MeV and about 4 cmwith a beam energy of 10 MeV. The penetration of e-beam is known toincrease slightly with increased irradiation temperatures. If electronirradiation is preferred, the desired depth of penetration can beadjusted based on the beam energy. Accordingly, gamma irradiation orelectron irradiation may be used based upon the depth of penetrationpreferred, time limitations and tolerable oxidation levels.

Ranges of acceptable dose rates are exemplified in InternationalApplication WO 97/29793. In general, the dose rates vary between 0.5Mrad/pass and 50 Mrad/pass. The upper limit of the dose rate depends onthe resistance of the polymer to cavitation/cracking induced by theirradiation.

If electron radiation is utilized, the energy of the electrons also is aparameter that can be varied to tailor the properties of the irradiatedpolymer. In particular, differing electron energies result in differentdepths of penetration of the electrons into the polymer. The practicalelectron energies range from about 0.1 MeV to 16 MeV giving approximateiso-dose penetration levels of 0.5 mm to 8 cm, respectively. Thepreferred electron energy for maximum penetration is about 10 MeV, whichis commercially available through vendors such as Studer (Daniken,Switzerland) or E-Beam Services New Jersey, USA). The lower electronenergies may be preferred for embodiments where a surface layer of thepolymer is preferentially cross-linked with gradient in cross-linkdensity as a function of distance away from the surface.

In accordance with another aspect of the invention, the polymericpreform also has a gradient of cross-link density in a directionperpendicular to the direction of irradiation, wherein a part of thepolymeric preform was preferentially shielded to partially blockradiation during irradiation in order to provide the gradient ofcross-link density, wherein the preferential shielding is used where agradient of cross-link density is desired and the gradient of cross-linkdensity is in a direction perpendicular to the direction of irradiationon the preferentially shielded polymeric preform, such as is disclosedin U.S. Pat. No. 7,205,339, the methodologies of which are herebyincorporated by reference.

Various methods of preferential shielding according to the invention aredescribed in more details in the following illustrative examples.Although the examples may represent only selected embodiments of theinvention, it should be understood that the following examples areillustrative and not limiting.

Preferential Shielding:

The selective, controlled manipulation of polymers using radiationchemistry can, in another aspect, be achieved by preferentialirradiation shielding. By using a shield or shields made of selectedmaterials, selected thicknesses, selected geometry's, selected areas andutilization of the shields in a selected order, the overall propertiesof the irradiated polymer may be controlled and tailored to achieve adesired result, particularly in view of alterations that can be made inthe type of irradiation, the irradiation dose, dose rate and exposuretime and temperature, as well as the methodology used (for example, IMS,WIR, CIR, CIR-SM and WIAM). Shielded irradiation can be used inconjunction with other methods such as varying the concentration profileof an antioxidant/anti-crosslinking agent in the polymeric material tocontrol crosslink density distribution.

a. Shield Material

The irradiation shield may be made from any material that will at leastshield in part polymer from the irradiation. Exemplary materials includeceramics, metals, and glass. Suitable ceramics include alumina andzirconia. Suitable metals include aluminum, lead, iron, and steel.Polymers also may be used as shields.

b. Shield Geometry's and Order

An irradiation shield may be provided in any shape, cross-section, orthickness.

It is well known in the at that the thickness of the shield willcontribute to the ability of the material to shield the irradiation.Accordingly, the thickness of the shield can be selected depending uponthe extent of shielding that is desired in the shielded portion. In thismanner, the depth of irradiation penetration can be controlled, or atotal shielding of irradiation of the covered areas can be achieved. Theiso-dose penetration (defined as the depth at which the dose equals thatat the e-beam incidence surface) and the dose-depth penetration profiledepend on the energy of the electrons used.

The irradiation of materials with electrons leads to the well knownbuilt-up of absorbed dose level as a function of distance away from theelectron beam incidence surface. This built-up of the absorbed dose isdue to the generation of secondary electrons following the collision ofthe incident electrons with the atoms of the host material. Thecollisions generate more electrons at the expense of loosing kineticenergy while increasing the effective absorbed dose level as theelectron flux travels into the material. At a critical depth, thekinetic energy loss reaches a level where the electron flux slows downand leads to an abrupt decay in the absorbed dose level. The depth atwhich the absorbed dose level is equal to that at the surface is calledthe iso-dose penetration depth. This penetration increases with theincreasing energy of the incident electrons. Provided herein are twomethods of determining the iso-dose penetration of 10 MeV electrons intoUHMWPE, namely dosimetry and determination of trans-vinlyeneunsaturations.

Thus, effect of irradiation and shielding can be controlled through thematerials used in the shield, the thickness of the shield (constant orvariable), the extent to which the shield covers the area of thematerial being irradiated (full or partial), the order of shielding andirradiation, the type and extent of irradiation, and polymer selection.

c. Complete Coverage Shielding

UHMWPE (GUR 1050) was covered by aluminum shield of varying thicknesses(1, 3, 5, 7, 9, 11, 13, 15 mm) and irradiated either at room temperatureor at 125° C. The irradiation was carried out at E-Beam Services(Cranbury, N.J.) using the 10/50 Impela linear electron acceleratoroperated at 10 MeV and 50 kW. To determine the penetration profile ofthe effects of e-beam, spatial variation in the trans-vinylene contentin the irradiated UHMWPE specimens was determined. The GUR 1050 UHMWPEhas no detectable trans-vinylene unsaturations. The ionizing radiation,e-beam in the present case, leads to the formation of trans-vinyleneunsaturations, the content of which varies linearly with absorbedradiation dose.

FIG. 13 shows a schematic of the shield/UHMWPE construct. Followingirradiation, the irradiated UHMWPE construct was machined in half andmicrotomed as shown in FIG. 14, The microtomed thin section was thenanalyzed using a BioRad UMA 500 infra-red microscope with an aperturesize of 100 μm by 50 μm as a function of depth away from theshield/UHMWPE interface at 1 mm increments. Each individual infra-redspectra was then analyzed by normalizing the area under thetrans-vinylene vibration at 965 cm⁻¹ to the that under the 1900 cm⁻¹after subtracting the respective baselines. The value obtained, that isthe trans-vinylene index (TVI), is directly proportional to the absorbedradiation dose level.

The following equation was used:

${TVI} = \frac{{\int_{950}^{980}{{A(w)}\ {\mathbb{d}w}}} - B_{1}}{{\int_{1850}^{1985}{{A(w)}\ {\mathbb{d}w}}} - B_{2}}$$B_{1} = \frac{\left\lbrack {{A(980)} + {A(950)}} \right\rbrack\left( {980 - 950} \right)}{2}$$B_{2} = \frac{\left\lbrack {{A(1850)} + {A(1985)}} \right\rbrack\left( {1985 - 1880} \right)}{2}$where A(w) is the infra-red absorbance measured at wave number, w, B₁ isthe area under the baseline of the trans-vinylene vibration and B₂ isthat of the baseline under the reference (1900 cm⁻¹) vibration.

FIG. 15 shows the variation of TVI in room temperature irradiated UHMWPEas a function of distance away from the shield/UHMWPE interface fordifferent shield thicknesses. FIG. 16 shows the same for the UHMWPE thatwas irradiated at 125° C. The figures clearly show that the penetrationof the effects of e-beam can be controlled by placing an aluminum shieldand by varying its thickness. The temperature at which the irradiationis being carried can also be used to change the profile of the beampenetration. This is illustrated in FIG. 17 where the variation in TVIwith depth is presented for three different shield thicknesses (1, 9,and 15 mm) and two irradiation temperatures (25° C. and 125° C.).

d. Partial Coverage Shielding

UHMWPE (GUR 1050) was covered by a 1 cm thick aluminum shield with around opening in the center, as shown in FIG. 18. The UHMWPE/shieldconstruct was then irradiated at 150° C. using the Van de Graafgenerator at the High Voltage Research Laboratories of MassachusettsInstitute of Technology (Cambridge, Mass.). This partial shieldingscheme should lead to the irradiation of the central part of the UHMWPEcylinder. To confirm this, the spatial distribution of the effects ofe-beam was determined by measuring the content of trans-vinyleneunsaturations as a function of distance away from the side-wall to thecenter of the UHMWPE disc in the direction perpendicular to the e-beamincidence direction.

The GUR 1050 UHMWPE has no detectable trans-vinylene unsaturations. Theionizing radiation, e-beam in the present case, leads to the formationof trans-vinylene unsaturations, the content of which varies linearlywith absorbed radiation dose.

Following irradiation, the irradiated UHMWPE cylinder was machined inhalf and microtomed as shown in FIG. 19. The microtomed thin section wasthen analyzed using a BioRad UMA 500 infra-red microscope with anaperture size of 100 μm by 50 μm as a function of depth away from thesidewall to the center of the irradiated UHMWPE disk at 1 mm increments.Each individual infra-red spectra was then analyzed by normalizing thearea under the trans-vinylene vibration at 965 cm⁻¹ to the that underthe 1900 cm⁻¹ after subtracting the respective baselines. The valueobtained, that is the trans-vinylene index (TVI), is directlyproportional to the absorbed radiation dose level.

The following equation was used:

${TVI} = \frac{{\int\limits_{950}^{980}{{A(w)}{\mathbb{d}w}}} - B_{1}}{{\int\limits_{1850}^{1985}{{A(w)}{\mathbb{d}w}}} - B_{2}}$$B_{1} = \frac{\left\lbrack {{A(980)} + {A(950)}} \right\rbrack\left( {980 - 950} \right)}{2}$$B_{2} = \frac{\left\lbrack {{A(1850)} + {A(1985)}} \right\rbrack\left( {1985 - 1880} \right)}{2}$where A(w) is the infra-red absorbance measured at wave number, w, B₁ isthe area under the baseline of the trans-vinylene vibration and B₂ isthat of the baseline under the reference (1900 cm⁻¹) vibration.

FIG. 20 shows the variation of TVI in the irradiated UHMWPE as afunction of distance away from the sidewall of the shielded andirradiated UHMWPE. Under the shielded region, the TVI level was nearzero; while the value under the unshielded region increased, indicatingthe presence of radiation in this region.

The effect of irradiation with a disc shaped shield on UHMWPE also isillustrated in FIG. 21 where an unirradiated UHMWPE (panel a) andshield-irradiated UHMWPE (panel b) are shown. When the irradiation iscarried out above the melting point of UHMWPE, which is the case here,the crystallinity decreases significantly and melt-irradiated UHMWPEbecomes more transparent. This transparency is apparent in Figure panelb, in the region where the shield was not covering the UHMWPE disc. Thedecrease in the crystallinity is also associated with a decrease inmodulus. Therefore, one can use the procedure described here tomanufacture different shaped UHMWPE with regions of lower modulus forspecific medical applications.

The shape and cross-section of the shield also plays an important rolein determining the properties of the irradiated polymer. Any shape andcross-section shield; or combination of shapes and cross-sections, maybe utilized to achieve a desired cross-link depth and pattern.

FIG. 28 illustrates some exemplary shield edge geometry's and thehypothesized irradiation penetration envelopes resulting therefrom areshown in FIG. 30. In particular, depiction (A) FIG. 28 show arectangular cross-section. The cross-link pattern, when there is a fullblocking of irradiation, leaves most of the area under the shielduncross-linked. However, there is a portion of the polymer under eachedge of the shield that is cross-linked due to the electron penetrationenvelope. This pattern is the result of the “teardrop” signature left byelectron radiation as it travels through the polymer. This signature isdepicted in FIG. 30. FIG. 29 illustrates the effect of an irradiationshield on the depth of penetration of electron radiation at 10 MeV.

Depictions (B), (C), (G) and (H) illustrate an inclined or declinedcross-section and the resultant cross-linking pattern. Depictions (D)and (E) illustrate a curved cross-section and the resultantcross-linking pattern. Other cross-sections are attainable according tothe teachings contained herein.

Illustrative examples of suitable shield geometry's, cross-sections, andthe use of shielding in sequence are shown in FIGS. 22-27 and 31. FIG.31, for example, illustrates the irradiation of a polymer preform usingboth a ring-shaped and disc-shaped shield in sequence. Using acombination of ring and discs shields is an exemplary method of usingshielding to impart different properties to the core and periphery of apolymer preform.

e. Complete Coverage Vs. Partial Coverage Shielding

“Complete” coverage shielding, denoting the use of a shield that coversthe entire surface of the polymer being irradiated, is characterized bya cross-linking gradient parallel to the direction of irradiation. Thatis, due to the shield (including, for example, a portion of the polymeritself), there will be differences in the degree of cross-linking,resulting in a gradient ranging from extensively cross-linked tonon-cross-linked, in the plane of the preform that is parallel to thevector that defines the direction of the radiation from the source tothe preform. Examples of complete coverage shielding are shown in FIGS.29, 33 and 34. In FIG. 33, the surface of the polymer is designed to beof sufficient thickness to act as a shield for the irradiation from theinner portion of the polymer. In other embodiments, other shields may beplaced on or over the surface of the polymer such that the depth ofpenetration of irradiation, as the resulting cross-linking, is affected.FIG. 34 shows a particular embodiment of complete coverage shielding inwhich the preform is rotated along an axis passing through the interiorof the preform. As FIG. 34 shows, this embodiment results in a gradientof cross-linking parallel to the vector that defines the direction ofthe radiation from the source to the preform and in which outer portionof the preform are more extensively cross-linked relative to the innerportion.

“Partial” coverage shielding, denoting the use of a shield that does notcover the entire surface of the polymer being irradiated, ischaracterized by a cross-linking gradient perpendicular to direction ofirradiation. That is, due to the shield, there will be differences inthe degree of cross-linking, ranging from extensively cross-linked tonon-cross-linked, in the plane of the preform that is perpendicular tothe vector that defines the direction of the radiation from the sourceto the preform. FIG. 32. Due to propagation of the electrons in theirradiated preform, a degree of cross-linking will occur under the outeredges of the shield, which are schematically depicted as tear drops inFIG. 30. Thus, where differential shielding has been performed, agradient of fuller cross-linking to comparatively lesser cross-linkingor no crosslinking will be observed in the plane represented by thedirectional arrow in (see FIG. 32). Thus, cross-linking will be greatestin the unshielded areas, begin to decrease at the interface of theshield and an unshielded (or lesser shielded) edge, and decreasefurther, or be absent altogether (depending upon the thickness andconsistency of the shield), at the inner portions under the shieldedarea.

Gradient of Antioxidant/Anti-Crosslinking Agent Distribution:

A gradient concentration refers in general to a gradient distribution ofan additive concentration throughout or a portion of a polymericpreform. A gradient concentration of antioxidant/anti-crosslinking agentrefers to a gradient of antioxidant/anti-crosslinking agent distributionthroughout or a portion of a polymeric preform. The gradient ofantioxidant distribution can be continuous or non-continuous throughoutor within a portion of the polymeric preform. Such as, a polymericpreform containing layers of consolidated UHMWPE and the preform has agradient of antioxidant distribution uniform throughout the preform orthe gradient of antioxidant distribution varies from one layer toanother. A gradient concentration of the antioxidant can be limited ordirected to an interface or a layer of polymeric material within apolymeric preform where there is a gradient of antioxidant distributionwithin a defined region.

A gradient of cross-link density and a gradient concentration ofantioxidant also can be obtained by extraction methods, such asdisclosed in WO 2008/092047, the methodologies of which are herebyincorporated by reference.

The terms “extraction” or “elution” of antioxidant from antioxidantcontaining consolidated polymeric material refers to partial or completeremoval of the antioxidant, for example, vitamin E, from theconsolidated polymeric material by various processes disclosed herein.For example, the extraction or elution of antioxidant can be done with acompatible solvent that dissolves the antioxidant contained in theconsolidated polymeric material. Such solvents include, but not limitedto, a hydrophobic solvent, such as hexane, heptane, or a longer chainalkane; an alcohol such as ethanol, any member of the propanol orbutanol family or a longer chain alcohol; or an aqueous solution inwhich an antioxidant, such as vitamin E is soluble. Such a solvent alsocan be made by using an emulsifying agent such as Tween 20, Tween 80,fatty acids, other surfactants or ethanol. The extraction or elution ofantioxidant from antioxidant containing consolidated polymeric materialis generally done prior to placement and/or implantation of thepolymeric material, or a medical implant comprising the antioxidantcontaining consolidated polymeric material, into the body.

Extraction of α-tocopherol from a polyethylene at a temperature belowthe melting temperature of the polyethylene can be achieved by placingthe polyethylene in an open or in a sealed chamber. A solvent or anaqueous solution also can be added in order to extract the a-tocopherolfrom polyethylene. The chamber is then heated below the melting point ofthe polyethylene, preferably between about room temperature to near themelting point, more preferably about 100° C. to about 137° C., morepreferably about 120° C., or more preferably about 130° C. If a sealedchamber is used, there will be an increase in pressure during heating.Because the polyethylene is cross-linked, only the crystalline regionsmelt. The chemical cross-links between chains remain intact and allowthe polyethylene to maintain its shape throughout the process despitesurpassing its melting temperature. Increasing pressure increases themelting temperature of the polymeric material. In this case,homogenization below the melt is performed under pressure above 137° C.,for example at about 145° C.

Extraction of α-tocopherol from a polyethylene at a temperature abovethe melting temperature of the polyethylene can be achieved by placingthe polyethylene in an open or in a sealed chamber. A solvent or anaqueous solution also can be added in order to extract the a-tocopherolfrom polyethylene. The chamber is then heated above the melting point ofthe polyethylene, preferably between about 137° C. to about 400° C.,more preferably about 137° C. to about 200° C., more preferably about137° C., or more preferably about 160° C. If a sealed chamber is used,there will be an increase in pressure during heating. Because thepolyethylene is cross-linked, only the crystalline regions melt. Thechemical cross-links between chains remain intact and allow thepolyethylene to maintain its shape throughout the process despitesurpassing its melting temperature. Since crystallites pose a hindranceto diffusion of α-tocopherol in polyethylene, increasing the temperatureabove the melting point should increase the rate of extraction ofα-tocopherol. Increasing pressure increases the melting temperature ofthe polymeric material.

“Metal Piece”, in accordance with the invention, the piece forming aninterface with polymeric material is, for example, a metal. The metalpiece in functional relation with polymeric material, according to thepresent invention, can be made of a cobalt chrome alloy, stainlesssteel, titanium, titanium alloy or nickel cobalt alloy, for example.

“Non-metallic, Piece”, in accordance with the invention, the pieceforming an interface with polymeric material is, for example, anon-metal. The non-metal piece in functional relation with polymericmaterial, according to the present invention, can be made of ceramicmaterial, for example.

The term “inert atmosphere” refers to an environment having no more than1% oxygen and more preferably, an oxidant-free condition that allowsfree radicals in polymeric materials to form cross links withoutoxidation during a process of sterilization. An inert atmosphere is usedto avoid O₂, which would otherwise oxidize the medical device comprisinga polymeric material, such as UHMWPE. Inert atmospheric conditions suchas nitrogen, argon, helium, or neon are used for sterilizing polymericmedical implants by ionizing radiation.

Inert atmospheric conditions such as nitrogen, argon, helium, neon, orvacuum are also used for sterilizing interfaces of polymeric-metallicand/or polymeric-polymeric in medical implants by ionizing radiation.

Inert atmospheric conditions also refer to an inert gas, inert fluid, orinert liquid medium, such as nitrogen gas or silicon oil.

“Anoxic environment” refers to an environment containing gas, such asnitrogen, with less than 21%-22% oxygen, preferably with less than 2%oxygen. The oxygen concentration in an anoxic environment also can be atleast about 1%, 2%, 4%, 6%, 8%, 10%, 12% 14%, 16%, 18%, 20%, or up toabout 22%, or any value thereabout or therebetween.

The term “vacuum” refers to an environment having no appreciable amountof gas, which otherwise would allow free radicals in polymeric materialsto form cross links without oxidation during a process of sterilization.A vacuum is used to avoid O₂, which would otherwise oxidize the medicaldevice comprising a polymeric material, such as UHMWPE. A vacuumcondition can be used for sterilizing polymeric medical implants byionizing radiation.

A vacuum condition can be created using a commercially available vacuumpump. A vacuum condition also can be used when sterilizing interfaces ofpolymeric-metallic and/or polymeric-polymeric in medical implants byionizing radiation.

A “sensitizing environment” or “sensitizing atmosphere” refers to amixture of gases and/or liquids (at room temperature) that containsensitizing gaseous and/or liquid component(s) that can react withresidual free radicals to assist in the recombination of the residualfree radicals. The gases maybe acetylene, chloro-trifluoro ethylene(CTFE), ethylene, or like. The gases or the mixtures of gases thereofmay contain noble gases such as nitrogen, argon, neon and like. Othergases such as, carbon dioxide or carbon monoxide may also be present inthe mixture. In applications where the surface of a treated material ismachined away during the device manufacture, the gas blend could alsocontain oxidizing gases such as oxygen. The sensitizing environment canbe dienes with different number of carbons, or mixtures of liquidsand/or gases thereof. An example of a sensitizing liquid component isoctadiene or other dienes, which can be mixed with other sensitizingliquids and/or non-sensitizing liquids such as a hexane or a heptane. Asensitizing environment can include a sensitizing gas, such asacetylene, ethylene, or a similar gas or mixture of gases, or asensitizing liquid, for example, a diene. The environment is heated to atemperature ranging from room temperature to a temperature below themelting point of the material.

In certain embodiments of the present invention in which the sensitizinggases and/or liquids or a mixture thereof, inert gas, air, vacuum,and/or a supercritical fluid can be present at any of the method stepsdisclosed herein, including blending, mixing, consolidating, quenching,irradiating, annealing, mechanically deforming, doping, homogenizing,heating, melting, and packaging of the finished product, such as amedical implant.

“Residual free radicals” refers to free radicals that are generated whena polymer is exposed to ionizing radiation such as gamma or e-beamirradiation. While some of the free radicals recombine with each otherto from cross-links, some become trapped in crystalline domains. Thetrapped free radicals are also known as residual free radicals.

According to one aspect of the invention, the levels of residual freeradicals in the polymer generated during an ionizing radiation (such asgamma or electron beam) is preferably determined using electron spinresonance and treated appropriately to reduce the free radicals.

“Sterilization”, one aspect of the present invention discloses a processof sterilization of medical implants containing polymeric material, suchas cross-linked UHMWPE. The process comprises sterilizing the medicalimplants by ionizing sterilization with gamma or electron beamradiation, for example, at a dose level ranging from about 25-70 kGy, orby gas sterilization with ethylene oxide or gas plasma.

Another aspect of the present invention discloses a process ofsterilization of medical implants containing polymeric material, such ascross-linked UHMWPE. The process comprises sterilizing the medicalimplants by ionizing sterilization with gamma or electron beamradiation, for example, at a dose level ranging from 25-200 kGy. Thedose level of sterilization is higher than standard levels used inirradiation. This is to allow cross-linking or further cross-linking ofthe medical implants during sterilization.

One aspect of the present invention discloses a process of increasingthe uniformity of the antioxidant following doping in polymericcomponent of a medical implant during the manufacturing process byheating for a time period depending on the melting temperature of thepolymeric material. For example, the preferred temperature is about 137°C. or less. Another aspect of the invention discloses a heating stepthat can be carried in the air, in an atmosphere, containing oxygen,wherein the oxygen concentration is at least about 1%, 2%, 4%, or up toabout 22%, or any value thereabout or therebetween. In another aspect,the invention discloses a heating step that can be carried while theimplant is in contact with an inert atmosphere, wherein the inertatmosphere contains gas selected from the group consisting of nitrogen,argon, helium, neon, or the like, or a combination thereof. In anotheraspect, the invention discloses a heating step that can be carried whilethe implant is in contact with a non-oxidizing medium, such as an inertfluid medium, wherein the medium contains no more than about 1% oxygen.In another aspect, the invention discloses a heating step that can becarried while the implant is in a vacuum.

The term “radiation generated heat” refers to the heat generated as aresult of conversion of some of the energies deposited by the electronsor gamma rays to heat during an irradiation process. Radiation generatedheating, which includes adiabatic and partially adiabatic heating,primarily depends on how well the sample is thermally insulated duringthe irradiation. With good thermal insulation, most of the heatgenerated is not lost to the surroundings and leads to the radiationgenerated heating (adiabatic and partially adiabatic) of the polymer toa higher temperature than the irradiation temperature. The heating alsocould be induced by using a high enough dose rate to minimize the heatloss to the surroundings. The radiation generated heating (includingadiabatic and partially adiabatic) depends on a number of processingparameters such as dose rate, initial temperature of the sample,absorbed radiation dose, and the like. Radiation generated heating(including adiabatic and partially adiabatic) is a result of theconversion of the radiation dose to heat in the irradiated sample. Ifthe temperature of the sample is high enough during melting, radiationgenerated heating (including adiabatic and partially adiabatic) resultsin melting of the crystals. Even when the initial temperature of thepolymer is low, for example, near room temperature or 40° C., theradiation generated heating (including adiabatic and partiallyadiabatic) can be high enough to increase the temperature of the polymerduring irradiation. If the initial temperature and radiation dose aretoo high, radiation generated heating (including adiabatic and partiallyadiabatic) may result in complete melting of the polymer.

It should be noted that in theoretical thermodynamics, “adiabaticheating” refers to an absence of heat transfer to the surroundings. Inthe practice, such as in the creation of new polymeric materials,“adiabatic heating” refers to situations where a sufficient majority ofthermal energy is imparted on the starting material and is nottransferred to the surroundings. Such can be achieved by the combinationof insulation, irradiation dose rates and irradiation time periods, asdisclosed herein and in the documents cited herein. Thus, what mayapproach adiabatic heating in the theoretical sense achieves it in thepractical sense. However, not all warm irradiation refers to an“adiabatic heating.” Warm irradiation also can have non-adiabatic orpartially (such as 10-75% of the heat generated are lost to thesurroundings) adiabatic heating.

In an aspect of this invention, room temperature irradiation refers thatthe polymeric material is at ambient temperature is not heated by anexternal heating element before or during irradiation. However, theirradiation itself may heat up the polymeric material. In some cases theradiation dose is lower, which only results in minor rise in temperaturein the polymeric material, and in some other cases the radiation dose ishigher, which results in large increases in temperature in the polymericmaterial. Similarly the dose rate also plays an important role in theheating of the polymeric material during irradiation. At low dose ratethe temperature rise is smaller while with larger dose rates theradiation imparted heating becomes more adiabatic and leads to largerincreases in the temperature of the polymeric material. In any of thesecases, as long as there is no other heating source other than radiationitself, the process is considered as room temperature irradiation.

In another aspect of this invention, there is described the heatingmethod of implants to increase the uniformity of the antioxidant. Themedical device comprising a polymeric raw material, such as UHMWPE, isgenerally heated to a temperature of about 137° C. or less following thestep of doping with the antioxidant. The medical device is kept heatedin the inert medium until the desired uniformity of the antioxidant isreached.

The term “below melting point” or “below the melt” refers to atemperature below the melting point of a polymeric material, forexample, polyethylene such as UHMWPE. The term “below melting point” or“below the melt” refers to a temperature less than about 145° C., whichmay vary depending on the melting temperature of the polymeric material,for example, about 145° C., 140° C. or 135° C., which again depends onthe properties of the polymeric material being treated, for example,molecular weight averages and ranges, batch variations, etc. The meltingtemperature is typically measured using a differential scanningcalorimeter (DSC) at a heating rate of 10° C. per minute. The peakmelting temperature thus measured is referred to as melting point, alsoreferred as transition range in temperature from crystalline toamorphous phase, and occurs, for example, at approximately 137° C. forsome grades of UHMWPE. It may be desirable to conduct a melting study onthe starting polymeric material in order to determine the meltingtemperature and to decide upon an irradiation and annealing temperature.Generally, the melting temperature of polymeric material is increasedwhen the polymeric material is under pressure.

The term “heating” refers to thermal treatment of the polymer at or to adesired heating temperature. In one aspect, heating can be carried outat a rate of about 10° C. per minute to the desired heating temperature.In another aspect, the heating can be carried out at the desired heatingtemperature for desired period of time. In other words, heated polymerscan be continued to heat at the desired temperature, below or above themelt, for a desired period of time. Heating time at or to a desiredheating temperature can be at least 1 minute to 48 hours to severalweeks long. In one aspect the heating time is about 1 hour to about 24hours. In another aspect, the heating can be carried out for any timeperiod as set forth herein, before or after irradiation. Heatingtemperature refers to the thermal condition for heating in accordancewith the invention. Heating can be performed at any time in a process,including during, before and/or after irradiation. Heating can be donewith a heating element. Other sources of energy include the environmentand irradiation.

The term “high temperature melting” refers to thermal treatment of thepolymer or a starting material to a temperature between about 200° C.and about 500° C. or more, for example, temperature of about 200° C.,about 250° C., about 280° C., about 300° C., about 320° C., about 350°C., about 380° C., about 400° C., about 420° C., about 450° C., about480° C. or more. Heating time at “high temperature melting” can be atleast 30 minutes to 48 hours to several weeks long. In one aspect the“high temperature melting” time is continued for about 1 minute to about48 hours or more. For example, the heating is continued for at least forone minute, 10 minutes, 20 minutes, 30 minutes, one hour, two hours,five hours, ten hours, 24 hours, or more.

The term “annealing” refers to heating or a thermal treatment conditionof the polymers in accordance with the invention. Annealing generallyrefers to continued heating the polymers at a desired temperature belowits peak melting point for a desired period of time. Annealing time canbe at least 1 minute to several weeks long. In one aspect the annealingtime is about 4 hours to about 48 hours, preferably 24 to 48 hours andmore preferably about 24 hours. “Annealing temperature” refers to thethermal condition for annealing in accordance with the invention.Annealing can be performed at any time in a process, including during,before and/or after irradiation.

In certain embodiments of the present invention in which annealing canbe carried out, for example, in an inert gas, e.g., nitrogen, argon orhelium, in a vacuum, in air, and/or in a sensitizing atmosphere, forexample, acetylene.

The term “contacted” includes physical proximity with or touching suchthat the sensitizing agent can perform its intended function.Preferably, a polymeric composition or preform is sufficiently contactedsuch that it is soaked in the sensitizing agent, which ensures that thecontact is sufficient. Soaking is defined as placing the sample in aspecific environment for a sufficient period of time at an appropriatetemperature, for example, soaking the sample in a solution of anantioxidant. The environment is heated to a temperature ranging fromroom temperature to a temperature below the melting point of thematerial. The contact period ranges from at least about 1 minute toseveral weeks and the duration depending on the temperature of theenvironment.

The term “non-oxidizing” refers to a state of polymeric material havingan oxidation index (A. U.) of less than about 0.5, according to ASTMF2102 or equivalent, following aging polymeric materials for 5 weeks inair at 80° C. oven. Thus, a non-oxidizing cross-linked polymericmaterial generally shows an oxidation index (A. U.) of less than about0.5 after the aging period.

The term “oxidatively stable” or “oxidative stability” or“oxidation-resistant” refers a state of polymeric material having anoxidation index (A. U.) of less than about 0.1 following aging polymericmaterials for 5 weeks in air at 80° C. oven. Thus, a oxidatively stableor oxidation-resistant cross-linked polymeric material generally showsan oxidation index (A. U.) of less than about 0.1 after the agingperiod.

The term “surface” of a polymeric material refers generally to theexterior region of the material having a thickness of about 1.0 μm toabout 2 cm, preferably about 1.0 mm to about 5 mm, more preferably about2 mm of a polymeric material or a polymeric sample or a medical devicecomprising polymeric material.

The term “bulk” of a polymeric material refers generally to an interiorregion of the material having a thickness of about 1.0 μm to about 2 cm,preferably about 1.0 mm to about 5 mm, more preferably about 2 mm, fromthe surface of the polymeric material to the center of the polymericmaterial. However, the bulk may include selected sides or faces of thepolymeric material including any selected surface, which may becontacted with a higher concentration of antioxidant.

Although the terms “surface” and “bulk” of a polymeric materialgenerally refer to exterior regions and the interior regions,respectively, there generally is no discrete boundary between the tworegions. But, rather the regions are more of a gradient-like transition.These can differ based upon the size and shape of the object and theresin used.

The term “doping” refers to a general process known in the art (see, forexample, U.S. Pat. Nos. 6,448,315 and 5,827,904). In this connection,doping generally refers to contacting a polymeric material with anantioxidant under certain conditions, as set forth herein, for example,doping UHMWPE with an antioxidant under supercritical conditions.

In certain embodiments of the present invention in which doping ofantioxidant is carried out at a temperature above the melting point ofthe polymeric material, the antioxidant-doped polymeric material can befurther heated above the melt or annealed to eliminate residual freeradicals after irradiation. Melt-irradiation of polymeric material inpresence of an antioxidant, such as vitamin E, can change thedistribution of the vitamin E concentration and also can change themechanical properties of the polymeric material. These changes can beinduced by changes in crystallinity and/or by the plasticization effectof vitamin E at certain concentrations.

According to one embodiment, the surface of the polymeric material iscontacted with little or no antioxidant and bulk of the polymericmaterial is contacted with a higher concentration of at least oneantioxidant.

According to another embodiment, the surface of the polymeric materialis contacted with no antioxidant and bulk of the polymeric material iscontacted with a higher concentration of at least one antioxidant.

According to one embodiment, the bulk of the polymeric material iscontacted with little or no antioxidant and surface of the polymericmaterial is contacted with a higher concentration of antioxidant.

According to another embodiment, the bulk of the polymeric material iscontacted with no antioxidant and surface of the polymeric material iscontacted with a higher concentration of antioxidant.

According to another embodiment, the surface of the polymeric materialand the bulk of the polymeric material are contacted with the sameconcentration of antioxidant.

According to one embodiment, the surface of the polymeric material maycontain from about 0 wt % to about 50 wt % antioxidant, preferably about0.001 wt % to about 10 wt %, preferably between about 0.01 wt % to about0.5 wt %, more preferably about 0.2 wt %. According to anotherembodiment, the bulk of the polymeric material may contain from about 0wt % to about 50 wt %, preferably about 0.001 wt % to about 10 wt %,preferably between about 0.01 wt % to about 0.5 wt %, more preferablyabout 0.2 wt %, preferably between about 0.2 wt % and about 1% wt %,preferably about 0.5 wt %.

According to one embodiment, the antioxidant/anti-crosslinkingagent-poor regions of the polymeric material may contain a totaladditive concentration from about 0 wt % to about 50 wt % antioxidant,preferably about 0.001 wt % to about 10 wt %, preferably between about0.01 wt % to about 0.5 wt %, more preferably about 0.05 wt %. Accordingto another embodiment, the antioxidant/anti-crosslinking agent-richregions of the polymeric material may contain from about 0 wt % to about50 wt %, preferably about 0.001 wt % to about 10 wt %, preferablybetween about 0.01 wt % to about 5 wt %, preferably between about 0.2 wt% and about 5% wt %, preferably about 1 wt %.

According to another embodiment, the antioxidant concentration in thepolymeric material can be about 1 ppm to about 10,000 ppm, preferablyabout 100 ppm, about 500 ppm, about 1000 ppm, about 2000 ppm, about 3000ppm, about 5000 ppm, or to any value thereabout or therebetween.

According to another embodiment, the radiation dose is adjusteddepending on the concentration of the antioxidant to achieve a desiredcross-link density. At higher antioxidant concentrations, generally ahigher dose level is required in order to reach the same cross-linkdensity.

According to another embodiment, the surface of the polymeric materialand the bulk of the polymeric material contain the same concentration ofantioxidant(s).

More specifically, consolidated polymeric material can be doped with anantioxidant by soaking the material in a solution of the antioxidant.This allows the antioxidant to diffuse into the polymer. For instance,the material can be soaked in 100% antioxidant. The material also can besoaked in an antioxidant solution where a carrier solvent can be used todilute the antioxidant concentration. To increase the depth of diffusionof the antioxidant, the material can be doped for longer durations, athigher temperatures, at higher pressures, and/or in presence of asupercritical fluid. This can be performed sequentially for differentantioxidants or doping can be done with more than one antioxidant at atime.

The antioxidant can be diffused to a depth of about 5 mm or more fromthe surface, for example, to a depth of about 3-5 mm, about 1-3 mm, orto any depth thereabout or therebetween.

The doping process can involve soaking of a polymeric material, medicalimplant or device with an antioxidant, such as vitamin E, for about halfan hour up to several days, preferably for about one hour to 24 hours,more preferably for one hour to 16 hours. The antioxidant can be at roomtemperature or heated up to about 137° C. and the doping can be carriedout at room temperature or at a temperature up to about 137° C.Preferably the antioxidant solution is heated to a temperature betweenabout 100° C. and 135° C. or between about 110° C. and 130° C., and thedoping is carried out at a temperature between about 100° C. and 135° C.or between about 110° C. and 130° C. More preferably, the antioxidantsolution is heated to about 120° C. and the doping is carried out atabout 120° C.

Doping with α-tocopherol through diffusion at a temperature above themelting point of the irradiated polymeric material (for example, at atemperature above 137° C. for UHMWPE) can be carried out under reducedpressure, ambient pressure, elevated pressure, and/or in a sealedchamber, for about 0.1 hours up to several days, preferably for about0.5 hours to 6 hours or more, more preferably for about 1 hour to 5hours. The antioxidant can be at a temperature of about 137° C. to about400° C., more preferably about 137° C. to about 200° C., more preferablyabout 137° C. to about 160° C.

The doping and/or the irradiation steps can be followed by an additionalstep of homogenization. The term “homogenization” refers to a heatingstep in air or in anoxic environment to improve the spatial uniformityof the antioxidant concentration within the polymeric material, medicalimplant or device. Homogenization also can be carried out before and/orafter the irradiation step. The heating may be carried out above orbelow or at the peak melting point. Antioxidant-doped or -blendedpolymeric material can be homogenized at a temperature below or above orat the peak melting point of the polymeric material for a desired periodof time, for example, the antioxidant-doped or -blended polymericmaterial can be homogenized for about an hour to several days at roomtemperature to about 400° C. Preferably, the homogenization is carriedout at 90° C. to 180° C., more preferably 100° C. to 137° C., morepreferably 120° C. to 135° C., most preferably 130° C. Homogenization ispreferably carried out for about one hour to several days to two weeksor more, more preferably about 12 hours to 300 hours or more, morepreferably about 280 hours, or more preferably about 200 hours. Morepreferably, the homogenization is carried out at about 130° C. for about36 hours or at about 120° C. for about 24 hours. The polymeric material,medical implant or device is kept in an inert atmosphere (nitrogen,argon, and/or the like), under vacuum, or in air during thehomogenization process. The homogenization also can be performed in achamber with supercritical fluids such as carbon dioxide or the like.The pressure of the supercritical fluid can be about 1000 to about 3000psi or more, more preferably about 1500 psi. It is also known thatpressurization increases the melting point of UHMWPE. A temperaturehigher than 137° C. can be used for homogenization below the meltingpoint if applied pressure has increased the melting point of UHMWPEbeyond 137° C.

Homogenization enhances the diffusion of the antioxidant fromantioxidant-rich regions to antioxidant poor regions. The diffusion isgenerally faster at higher temperatures. At a temperature above themelting point the hindrance of diffusion from the crystalline domains iseliminated and the homogenization occurs faster. Melt-homogenization andsubsequent recrystallization may reduce the mechanical properties mostlydue to a decline in the crystallinity of the polymer. This may beacceptable or even desirable for certain applications. For example,applications where the decline in mechanical properties is not desirablethe homogenization can be carried out below the melting point.Alternatively, below or above the melt homogenized samples may besubjected to high pressure crystallization to further improve theirmechanical properties.

The polymeric material, medical implant or device is kept in an inertatmosphere (nitrogen, argon, neon, and/or the like), under vacuum, or inair during the homogenization process. The homogenization also can beperformed in a chamber with supercritical fluids such as carbon dioxideor the like. The pressure of the supercritical fluid can be 1000 to 3000psi or more, more preferably about 1500 psi. The homogenization can beperformed before and/or after and/or during the diffusion of theantioxidant.

In one embodiment, the invention discloses:

1. Starting material can be: Homopolymer, UHMWPE, other polyolefins,copolymers etc.; Blended with vitamin E; Doped with vitamin E; Blendedwith antioxidants; Doped with antioxidants; Blended of polymers;Gradients of antioxidant etc., and the like.

2. Heating include: Annealing below melt, Melting, and/or Melting at300° C. (melt above the peak melting point in the respective medium);and all of the above in water, steam, air, inert, sensitizing gas,reduced oxygen environment, in antioxidant, in antioxidant solutions, orsupercritical fluid(s).

3. Post-Irradiation treatments include: Heating (anneal or melt Or meltat 300° C.), Doping with antioxidant, High pressure crystallization(HPC), High pressure annealing (HPA), Deformation, and/or Low pressureannealing (LPA), and Low pressure crystallization (LPC).

4. Sterilization by methods including: Gamma, e-beam, x-ray, Gas plasma,and Ethylene oxide.

In another embodiment, the invention discloses:

1. Heating of the Starting Material and Pressurize, cool under pressure.

2. Heating of the Starting Material then HPC, HPA, Deformation, LPA, orLPC followed by Irradiation, and optionally followed by Post-IrradiationTreatments.

3. Irradiation of the Starting Material then heat and optionallyfollowed by post-irradiation treatments (for example, HPC).

4. Heat the Starting Material then Irradiation, and optionally followedby Post-Irradiation Treatments.

Each composition and aspects, and each method and aspects, which aredescribed above can be combined with another in various mannersconsistent with the teachings contained herein. According to theembodiments and aspects of the inventions, all methods and the steps ineach method can be applied in any order and repeated as many times in amanner consistent with the teachings contained herein.

The invention is further described by the following examples, which donot limit the invention in any manner.

EXAMPLES

Vitamin E:

Vitamin E (Acros™ 99% D-α-Tocopherol, Fisher Brand), was used in theexperiments described herein, unless otherwise specified. The vitamin Eused is very light yellow in color and is a viscous fluid at roomtemperature. Its melting point is 2-3° C.

Determination of Vitamin E Index (A.U.):

Fourier transform infrared spectroscopy (FUR) is used to quantify theVitamin E content in the UHMWPE. The FTIR, in other words also known asinfra-red microscopy, is used to quantify the Vitamin E content bymeasuring the vitamin E index, which is a dimensionless parameter.

The absorption peak associated with the alpha-tocopherol is located at1265 cm-1, which is then normalized with a methylene peak at 1895 cm-1.This ratio is reported as a vitamin E index.

The sample is prepared by microtoming a slice between 100 and 200micrometers thick through the thickness of the sample. The section mustbe microtomed orthogonally to the scan direction to prevent spreadingthe alpha-tocopherol in the through-thickness direction. The slice ismounted on the translating stage of a FTIR microscope, and FTIR spectraare collected a specified intervals from the surface into the bulk ofthe sample.

The vitamin B index can be converted into an absolute concentration bycomparing the index to a calibration curve prepared from UHMWPE sectionscontaining known amounts of Vitamin E.

Example 1. High Temperature Melting of UHMWPE Followed by High PressureCrystallization (HPC)

Slab compression molded (CM) and ram extruded (RE) blocks of UHMWPE(GUR1050, Orthoplastics, Lancashire, UK) were placed each in a stainlesssteel pouch, which was closed but not sealed. The pouch was placed incontact with the platens of a molding press (3895, Carver, Wabash,Ind.). Argon gas was constantly purged through the pouch while theplatens were heated. The sample was brought to 300° C. and kept at thistemperature under argon purge for 5 hours. Then, it was cooled underargon purge to about room temperature by shutting the heater off. Thecooled samples were then placed in a pressure chamber in water. Thechamber was sealed and the temperature was increased to 180° C. Thesample was kept at about 10,000 psi and 180° C. for 5 hours. The, thechamber was pressurized to 45,000 psi by pumping water and the samplewas kept at approximately 45,000 psi and 180° C. for at least 5 hours.Then, the chamber was cooled while maintaining pressure to below themelting point of UHMWPE at ambient pressure, i.e. approximately 137° C.,more often to room temperature. Then, the pressure was released and thesample was taken out of the chamber. Thin sections (3.2 mm-thick) weremachined from the high temperature melted and high temperature meltedand subsequently high pressure crystallized UHMWPE.

Control samples were untreated CM and RE UHMWPE and high pressurecrystallized (HPC) CM and RE UHMWPEs without prior high temperaturemelting.

Tensile mechanical properties were tested using Type V dog-bone-shapedsamples stamped out of these thin sections at 10 min/min according toASTM D-638. The elongation-to-break (EAB) was measured using a laserextensometer. The work-to-failure (WF) was calculated as the area underthe engineering stress-strain curve. The IZOD single-notch impact testswere done according to ASTM F648 (Orthoplastics, Lancashire, UK).

TABLE 1 Mechanical properties of high temperature melted and highpressure crystallized UHMWPE UTS IZOD impact (MPa) EAB (%) E (GPa) YS(MPa) Strength (kJ/m²) Work to failure (kJ/m²) Slab compression molded(CM) UHMWPE Untreated 51 ± 3 442 ± 20 1.3 ± 0.3 22 ± 1 127 ± 7 2995 ±267 HPC 60 ± 2 359 ± 11 NA 24 ± 1 HTM 47 ± 4 654 ± 36 2.4 ± 0.6 22 ± 1148 ± 3 4294 ± 296 HTM HPC 43 ± 2 543 ± 53 4.3 ± 1.6 25 ± 1 3283 ± 232Ram extruded (RE) UHMWPE Untreated 53 ± 6 391 ± 42 1.1 ± 0.6 20 ± 1 HPC61 ± 6 323 ± 23 5.5 ± 1.0 25 ± 1 HTM 44 ± 2 484 ± 42 2.5 ± 0.6 23 ± 1HTM HPC 53 ± 2 537 ± 5  4.5 ± 0.5 30 ± 1

TABLE 2 Crystallinity (X_(c)), peak melting point (PMT) of HTM and HTMHPC UHMWPE compared to control UHMWPEs. X_(c) (%) PMT (° C.) Slabcompression molded (CM) UHMWPE Untreated 53 ± 3 135.1 ± 0.0 HPC 72 ± 4144.3 ± 0.6 HTM 56 ± 1 134.9 ± 0.2 HTM HPC 67 ± 1 138.8 ± 0.7 Ramextruded (RE) UHMWPE Untreated 51 ± 4 135.1 ± 0.1 HPC 68 ± 3 146.4 ± 0.7HTM 62 ± 1 135.0 ± 0.1 HTM HPC 80 ± 1 144.3 ± 0.7

Crystallinity each) was measured by differential scanning calorimetryfrom −20° C. to 180° C. at a heating rate of 10° C./min. Thecrystallinity was determined by normalizing the enthalpy of fusion bythe enthalpy of fusion of 100% crystalline polyethylene; 291 J/g.

Sets of data were compared using Student t-test with unequal variance.Statistical significance was attributed for p<0.05.

The tensile mechanical properties of untreated UHMWPE, high temperaturemelted (HTM) UHMWPE, and high temperature melted, high pressurecrystallized (HTM HPC) UHMWPE are shown in Table 1. The results showedthat melting UHMWPE at 300° C. increased elongation significantly. Thecrystallinity was also increased (Table 2), resulting in a toughmaterial with improved elongation. High pressure crystallizationfollowing melting at 300° C. increased crystallinity and peak meltingpoint substantially for both ram extruded and compression molded UHMWPE,resulting in a highly crystalline UHMWPE (Table 2) with substantiallyimproved elongation. In addition, the modulus of melted and highpressure crystallized UHMWPE was less than non-melted high pressurecrystallized UHMWPE.

Example 2. High Temperature Melting of UHMWPE Followed by HPC andIrradiation

Slab compression molded (CM) and ram extruded (RE) blocks of virginUHMWPE and 0.15 wt % vitamin E-blended, compression molded UHMWPE areplaced each in a stainless steel pouch, which is closed but not sealed.The pouch is placed in contact with the platens of a molding press.Argon gas is constantly purged through the pouch while the platens areheated. The sample is brought to 300° C. and kept at this temperatureunder argon purge for 5 hours. Then, it is cooled under argon purge toabout room temperature. The cooled samples are then placed in a pressurechamber in water. The chamber is sealed and the temperature is increasedto 180° C. The sample is kept at about 10,000 psi and 180° C. for 5hours. The, the chamber is pressurized to 45,000 psi by pumping waterand the sample is kept at approximately 45,000 psi and 180° C. for atleast 5 hours. Then, the chamber is cooled while maintaining pressure tobelow the melting point of UHMWPE at ambient pressure, i.e.approximately 137° C., more often to room temperature. Then, thepressure is released and the sample is taken out of the chamber. Then,high temperature melted and subsequently high pressure crystallizedUHMWPE is irradiated at 25, 50, 100 and 150 kGy by electron beamirradiation.

Example 3. High Temperature Melting of Highly Cross-Linked UHMWPE

Slab compression molded GUR1050 UHMWPE that had been irradiated to100-kGy was used. Approximately 4 cm-thick blocks were placed inpre-heated inert gas convection oven (LLD1-16N-3, Despatch Inc., MN) at300 or 320° C. The samples were kept at temperature under nitrogen flowfor 1, 5 or 12 hours, after which the samples were cooled under nitrogenflow to below approximately 60° C. before taking the samples out of theoven.

Tensile testing was performed on dog-bones (Type V, ASTM D-638) stampedout of 3.2 mm-thick sections machined from high temperature meltedUHMWPEs. Testing was performed at 10 mm/min (MTS Insight, Eden Prairie,Minn.). Elongation to break (EAB) was determined by using a laserextensometer. Work to failure was determined as the area under theengineering stress-strain curves. The IZOD single-notch impact testswere done according to ASTM F648 (Orthoplastics, Lancashire, UK).Ultimate tensile strength (UTS) and elastic modulus (E) were alsomeasured.

Wear rates were determined by pin-on-disc wear testing on acustom-designed bidirectional wear tester (see Bragclon C R, O'Connor DO, Lowenstein J D, Jasty M, Biggs S A, Harris W H. A new pin-on-discwear testing method for simulating wear of polyethylene on cobalt-chromealloy in total hip arthroplasty. Journal of Arthroplasty 2001: 41(2):795-808), Testing was performed in undiluted, preserved bovine serum at2 Hz for 2 million cycles (MC) with gravimetric assessment of wear atapproximately every 500, 0.000 cycles. Wear rate was determined as alinear regression of weight loss as a function of number of cycles from0.5 to 2 MC.

Thin sections (150 μm-thick) were microtomed and analyzed using FourierTransform Infrared Spectroscopy (FTIR). A vinyl index was calculatedusing the area under 880-920 cm⁻¹ and normalizing it to the area under1895 cm⁻¹.

TABLE 3 High temperature melting (HTM) and elongation of unirradiatedUHMWPE as a function of increasing melting time. Wear rate IZOD impactUTS (MPa) EAB (%) E (GPa) YS (MPa) (mg/MC) strength (kJ/m²) No irr. 59 ±5 401 ± 15 1.3 ± 0.3 21 ± 1 10.2 ± 0.9 127 ± 7 No irr., 300° C., 1 hr 49± 1 541 ± 19 1.2 ± 0.2 19 ± 1  90 ± 3 No irr., 300° C. 5 hr 58 ± 5 720 ±14 1.6 ± 0.3 22 ± 1 148 ± 3 No irr., 300° C., 12 hr 52 ± 2 889 ± 26 1.6± 0.2 21 ± 1 118 ± 6 No irr., 320° C., 1 hr 60 ± 3 809 ± 44 1.6 ± 0.2 22± 1   67 ± 13 No irr., 320° C., 5 hr 44 ± 4  922 ± 217 2.6 ± 0.5 21 ± 2134 ± 1

TABLE 4 High temperature melting (HTM) and the elongation of 100-kGyirradiated UHMWPE as a function of increasing melting time. Wear rateIZOD impact UTS (MPa) EAB (%) E (GPa) YS (MPa) (mg/MC) strength (kJ/m²)100-kGy 50 ± 4 244 ± 19 24 ± 1 −2.3 ± 0.2  74 ± 2 100-kGy, 300° C., 1 hr49 ± 1 386 ± 19 1.8 ± 0.2 19 ± 1 −2.7 ± 1.0 149 ± 5 100-kGy, 300° C., 5hr 44 ± 3 527 ± 29 1.7 ± 0.1 20 ± 1 102 ± 7 100-kGy, 300° C., 12 hr 42 ±5 601 ± 60 1.8 ± 0.3 19 ± 0 −5.9 ± 1.4  99 ± 6 100-kGy, 320° C., .1 hr42 ± 2 587 ± 22 2.3 ± 0.2 21 ± 0  97 ± 5 100-kGy, 320° C., 5 hr 41 ± 2872 ± 25 3.1 ± 0.2 21 ± 0  33 ± 4

High temperature melting (HTM) increased the elongation of bothunirradiated and 100-kGy irradiated UHMWPE both compared to untreatedUHMWPE and as a function of increasing melting time (Table 3 and Table4). The crystallinity of unirradiated UHMWPEs melted at 300° C. did notchange with increasing melting time, but the vinyl index, which is anindicator of increased chain ends, increased (Table 5). Crystallinity ofboth unirradiated and 100-kGy irradiated UHMWPEs high temperature meltedat 320° C. were substantially higher than those melted at 300° C. (Table5 and Table 6). The vinyl index of irradiated UHMWPE was higher afterhigh temperature melting when compared to unirradiated UHMWPE.

There are two mechanisms expected to be prevalent in high temperaturemelted UHMWPEs; the first is the increased self-diffusion of polymerchains across grain boundaries at the high temperature, the other isincreased chain scissioning due to degradation at high temperature. Itis possible that the high crystallinity accompanying high vinyl indicesin some samples is due to the recrystallization of broken chains.However; shorter time melting of unirradiated UHMWPE resulted in bothhigh UTS due to increased diffusion/entanglement of chains, higherelongation to break, higher work to failure without the detriment ofincreased chain scission, for example 300° C. for 5 hours and 320° C.for 1 hr.

TABLE 5 Properties of high temperature melted UHMWPEs. Peak meltingCross-link Wear rate Crystallinity (%) point (° C.) Vinyl index density(mol/m³) (mg/MC) No irr. — 10.2 ± 0.9 No irr., 300° C., 1 hr 56 ± 1 134± 0 0.02 — No irr., 300° C., 5 hr 57 ± 2 135 ± 0 0.04 — No irr., 300°C., 12 hr 57 ± 1 135 ± 0 0.06 — No irr,, 320° C., 1 hr 63 ± 2 134 ± 00.05 — No irr., 320° C., 5 hr 69 ± 1 133 ± 0 0.09 —

TABLE 6 Properties of 100-kGy irradiated and high temperature meltedUHMWPEs. Peak Crystallinity melting Vinyl Cross-link Wear rate (%) point(° C.) index density (mol/m³) (mg/MC) 100-kGy 2.29 ± 1.0 100-kGy, 300°C., 1 hr 45 ± 1 132 ± 0 0.02 109 ± 3 2.74 ± 1.0 100-kGy, 300° C., 5 hr55 ± 1 130 ± 0 0.06  54 ± 1 100-kGy, 300° C., 12 hr 54 ± 0 132 ± 0 0.07 45 ± 2 5.86 ± 1.4 100-kGy, 320° C., 1 hr 58 ± 0 132 ± 0 0.09  45 ± 2100-kGy, 320° C., 5 hr 60 ± 1 131 ± 0 0.12  20 ± 0

The work-to-failure, an indicator of plasticity, increased as a functionof time at melting temperature (FIG. 35). This suggested that there is abalance between chain diffusion and polymer degradation, which allowsthe properties to improve for a period of time at the high meltingtemperature.

The weight loss as a function of temperature at the very hightemperatures of melting was measured by using a thermal gravimetricanalyzer (Q500, TA Instruments, New Castle, DL), heating to temperatureat 20° C./min and staying isothermal at the high temperature for thedesired duration. This experiment was performed on unirradiated UHMWPE,65-kGy and 100-kGy e-beam irradiated UHMWPEs at 280, 300, 320 and 340°C. for 24 hours. The weight loss curve most often displayed an initialweight loss within the heating period (first 10 minutes), then eitherequilibrated or continued at a steady pace (FIGS. 36, 37, and 38).

The initial weight loss during the heating period is attributed as theloss of volatiles and small molecular weight impurities in UHMWPE. Afterthis initial period, both unirradiated and irradiated UHMWPEs showedfaster weight loss and higher overall weight loss at the end of the 24hour period with increasing temperature. This suggests that there isincreasing degradation of the polymer with increasing temperature.

Example 4. High Temperature Melting of Vitamin E-Blended UHMWPE

Slab compression molded (CM) UHMWPE blended with 0.15 wt % vitamin E(GUR1050, Orthoplastics, Lancashire, UK) and 0.2 wt % vitamin E (Zimmer,Inc.) were placed each in a stainless steel pouch, which was closed butnot sealed. The pouch was placed in contact with the platens of amolding press (3895, Carver, Wabash, Ind.). Argon gas was constantlypurged through the pouch while the platens were heated. The samples werebrought to 300° C. and kept at this temperature under argon purge for 5hours. Then, they were cooled under argon purge to about roomtemperature by shutting the heater off.

TABLE 7 Ultimate tensile strength (UTS), elongation to break (EAB),Young's Modulus (B) and yield strength (YS) of HTM vitamin B-blendedUHMWPE. UTS (MPa) EAB (%) E (GPa) YS (MPa) 0.15 wt % 54.0 ± 6.4 386 ± 201.5 ± 0.3 21 ± 1 0.15 wt % HTM 52.0 ± 3.6 462 ± 39 1.0 ± 0.3 20 ± 1  0.2wt % HTM 56.4 ± 4.9 546 ± 94 0.9 ± 0.1 20 ± 1

Elongation of vitamin E-blended UHMWPEs increased through HTM withoutsignificant loss of strength (Table 7).

Example 5. High Temperature Melting Followed by Radiation Cross-Linkingand Post-Irradiation Melting

Slab compression molded (CM) blocks of UHMWPE (GUR1050, Orthoplastics,Lancashire, UK) were placed each in a stainless steel pouch, which wasclosed but not sealed. The pouch was placed in contact with the platensof a molding press (3895, Carver, Wabash, Ind.). Argon gas wasconstantly purged through the pouch while the platens were heated. Thesample was brought to 300° C. and kept at this temperature under argonpurge for 5 hours. Then, it was cooled under argon purge to about roomtemperature by shutting the heater off. The cooled blocks wereirradiated by electron beam irradiation (2.5 MeV, High voltage researchlaboratories, MIT, Cambridge, Mass.) to 25, 50, 100 and 150 kGy. Thinsections (3.2 mm-thick) were machined from the high temperature meltedand subsequently irradiated UHMWPE. A separate irradiated block of eachradiation dose was melted at 170° C. in a vacuum oven; yet anotherseparate block of each radiation dose was melted as described above at300° C. under argon purge.

Tensile testing was performed on dog-bones (Type V, ASTM D-638) stampedout of 3.2 mm-thick sections machined from high temperature meltedUHMWPEs. Testing was performed at 10 mm/min (MTS Insight, Eden Prairie,Minn.). Elongation to break (EAB) was determined by using a laserextensometer. Work to failure was determined as the area under theengineering stress-strain curves. The IZOD single-notch impact testswere done according to ASTM F648 (Orthoplastics, Lancashire, UK).Ultimate tensile strength (UTS) and elastic modulus (E) were alsomeasured.

Wear rates were determined by pin-on-disc wear testing on acustom-designed bidirectional wear tester (see Bragdon C R, O'Connor DO, Lowenstein J D, Jasty M, Biggs S A, Harris W H. A new pin-on-discwear testing method for simulating wear of polyethylene on cobalt-chromealloy in total hip arthroplasty. Journal of Arthroplasty 2001: 41(2):795-808). Testing was performed in undiluted, preserved bovine serum at2 Hz for 2 million cycles (MC) with gravimetric assessment of wear atapproximately every 500,000 cycles. Wear rate was determined as a linearregression of weight loss as a function of number of cycles from 0.5 to2 MC.

Crosslink density measurements of cross-linked UHMWPE (n=3 each) wereperformed on small samples (approximately 3×3×3 mm). The samples wereweighed before swelling in xylene at 130° C. and they were weighedimmediately after swelling in xylene. Therefore, the amount of xyleneuptake was determined gravimetrically, then converted to volumetricuptake by dividing by the density of xylene; 0.75 g/cc. By assuming thedensity of polyethylene to be approximately 0.99 glee, the volumetricswell ratio of crosslinked UHMWPE was then determined. The cross-linkdensity was calculated using the swell ratio as described previously(Muratoglu et al. Biomaterials 20:1463-1470 (1999)) and is reported asmol/m³.

The elongation of high temperature melted and irradiated UHMWPE wasincreased compared to irradiated UHMWPE (Table 8).

TABLE 8 Ultimate tensile strength (UTS), elongation to break (EAB),Young's Modulus (E) and yield strength (YS) of HTM + Irradiation + HTMUHMWPE. Cross-link UTS EAB E density (MPa) (%) (GPa) (mol/m³) No irr. 51± 3 442 ± 20 1.3 ± 0.3 — 25 kGy 46 ± 2 376 ± 20 3.0 ± 0.0  95 ± 0 50 kGy45 ± 6 321 ± 95 3.1 ± 0.9 120 ± 2 100 kGy 38 ± 5 249 ± 13  3.4 ± 10.3152 ± 3 150 kGy 36 ± 1 202 ± 11 4.3 ± 0.4 186 ± 2 25 kGy + HTM 43 ± 4878 ± 96 2.0 ± 0.8  6 ± 0 50 kGy + HTM 46 ± 3  717 ± 115 1.7 ± 1.1  21 ±1 100 kGy + HTM 48 ± 1  686 ± 109  1.4 ± 10.5  43 ± 1 150 kGy + HTM 37 ±3 417 ± 44 2.6 ± 0.5  68 ± 1 HTM 47 ± 4 654 ± 36 2.4 ± 0.6   24 ± 10HTM + 25 kGy 54 ± 3 487 ± 60 1.9 ± 0.3 NT HTM + 50 kGy NA NA NA 116 ± 5HTM + 100 kGy 47 ± 2 326 ± 56 2.2 ± 0,4  125 ± 36 HTM + 150 kGy 48 ± 2280 ± 17 2.6 ± 0.3 169 ± 5 HTM + 25 kGy + HTM 43 ± 4 878 ± 96 2.0 ± 0.8 6 ± 0 HTM + 50 kGy + HTM 46 ± 3  717 ± 115 1.7 ± 1.1  11 ± 1 HTM + 100kGy + HTM 48 ± 1  686 ± 109 1.4 ± 0.5  22 ± 1 HTM + 150 kGy + HTM 36 ± 3416 ± 44 2.6 ± 0.5  50 ± 2 HTM + 25 kGy + 170° C. 48 ± 2 389 ± 9  1.0 ±0.2  85 ± 5 HTM + 50 kGy + 170° C. 47 ± 1 446 ± 12 1.3 ± 0.1 NT HTM +100 kGy + 170° C. 43 ± 1 320 ± 7  1.5 ± 0.1 NT HTM + 150 kGy + 170° C.36 ± 1 276 ± 4  1.8 ± 0.1 169 ± 5

100-key irradiated and 150-key irradiated UHMWPEs were similarly meltedin a pre-heated inert gas convection oven (LLD1-16N-3, Despatch Inc.,MN) at 300 or 320° C. The samples were kept at temperature undernitrogen flow for 5 hours, after which the samples were cooled undernitrogen flow to below approximately 60° C. before taking the samplesout of the oven.

The cross-link density of 100 kGy irradiated UHMWPE was 152±5 mol/m³ andits wear rate was −2.7±0.8 mg/million cycle. The cross-link density ofvirgin UHMWPE melted at 300° C. for 5 hours and subsequently irradiatedto 150 kGy was 124±7 mol/m³ and its wear rate was −1.9±0.3mg/million-cycle. Current understanding of wear reduction in UHMWPEdictates that decreased cross-link density results in increased wearrate. In this material which was high temperature melted beforeradiation cross-linking, the wear rate was decreased despite a decreasein cross-link density.

In addition, the IZOD impact strength of 100 kGy irradiated UHMWPE was77±3 kJ/m² and that of 150 kGy irradiated UHMWPE was 62±3 kJ/m². Thesevalues represented a decrease from that of unirradiated UHMWPE, whoseIZOD impact strength was 127±7 kJ/m² as a function of increasingradiation dose. For UHMWPE melted at 300° C. for 5 hours andsubsequently irradiated to 150 kGy, the impact strength was 83±2 kJ/m²,Therefore, high temperature melting the UHMWPE before radiationcross-linking not only increased its wear resistance but also itsfracture toughness.

Example 6. High Temperature Melting of Vitamin E-Blended UHMWPE Followedby Radiation Cross-Linking

Vitamin E-blended. UHMWPE (0.1 wt % and 0.2 wt %) was prepared by mixingGUR1050 UHMWPE powder with a 10 wt % isopropyl alcohol solution ofvitamin E and subsequently drying the powder at 60° C. Then the powderwas consolidated into pucks (10 cm diameter, 1 cm thickness) using alaboratory press (3895, Carver, Wabash, Ind.). The pucks were then hightemperature melted in a convection oven equipped with a nitrogen purge(LLD1-16N-3, Despatch Inc., MN) at 300° C. or 320° C. for 5 hours andwere cooled down under nitrogen purge to room temperature. Then, thehigh temperature melted pucks were packaged in vacuum and irradiated byelectron-beam irradiation (Iotron, Vancouver, BC) to 150 kGy at 50kGy/pass.

Crosslink density measurements of cross-linked UHMWPE (n=3 each) wereperformed on small samples (approximately 3×3×3 mm). The samples wereweighed before swelling in xylene at 130° C. and they were weighedimmediately after swelling in xylene. Therefore, the amount of xyleneuptake was determined gravimetrically, then converted to volumetricuptake by dividing by the density of xylene; 0.75 g/cc. By assuming thedensity of polyethylene to be approximately 0.99 g/cc, the volumetricswell ratio of crosslinked UHMWPE was then determined. The cross-linkdensity was calculated using the swell ratio as described previously(Muratoglu et al. Biomaterials 20:1463-1470 (1999)) and is reported asmol/m³.

Tensile mechanical properties were tested using Type V dog-bone-shapedsamples stamped out of these thin sections at 10 mm/min according toASTM D-638. The elongation to break was measured using a laserextensometer. The work to failure (WF) was calculated as the area underthe engineering stress-strain curve. Ultimate tensile strength (UTS) andelastic modulus (E) were also measured. The IZOD single-notch impacttests were done according to ASTM F648 (Orthoplastics, Lancashire, UK).

Crystallinity (n=3 each) was measured by differential scanningcalorimetry from −20° C. to 180° C. at a heating rate of 10° C./min. Thecrystallinity was determined by normalizing the enthalpy of fusion bythe enthalpy of fusion of 100% crystalline polyethylene; 291 J/g.

Thin sections (150 μm-thick) were microtomed and analyzed using FourierTransform Infrared Spectroscopy (FTIR). A vinyl index was calculatedusing the area under 880-920 cm⁻¹ and normalizing it to the area under1895 cm⁻¹.

TABLE 9 Crystallinity and peak melting point of high temperature meltedirradiated vitamin E-blended UHMWPEs. Crystallinity Peak melting Vinyl(%) point (° C.) index 0.1 wt % + 150-kGy 60 ± 0 139.4 0.01 0.1 wt % +300° C., 5 hr + 150 kGy 60 ± 1 138.8 0.01 0.1 wt % + 320° C., 5 hr + 150kGy 67 ± 0 137.3 0.03 0.2 wt % + 150-kGy 60 ± 1 139.3 0.01 0.2 wt % +300° C., 5 hr + 150 kGy 62 ± 1 138.9 0.01 0.2 wt % + 320° C., 5 hr + 150kGy 66 ± 1 137.8 0.02

High temperature melting prior to irradiation of vitamin E-blendedUHMWPE resulted in a material with increased elongation to break (EAB).At 300° C., 5 hours of melting gave a material with comparable ultimatetensile strength to irradiated UHMWPE without high temperature treatmentwith much improved elongation to break and decreased modulus. Incontrast, at 320° C., crystallinity and modulus were increased but notaccompanied by an increase in strength, suggesting that there wasincreased chain scissioning and re-crystallization in these samples(Tables 9 and 10).

TABLE 10 Ultimate tensile strength (UTS), elongation to break (EAB),Young's Modulus (E) and yield strength (YS) of HTM vitamin E-blendedUHMWPE. UTS E YS IZOD Impact (MPa) EAB (%) (GPa) (MPa) strength (kJ/m²)100 kGy 50 ± 4 303 ± 12 1.8 ± 0.2 21 ± 1 74 ± 3 150 kGy 48 ± 2 266 ± 192.0 ± 0.5 21 ± 1 62 ± 3 0.1 wt % + 150-kGy 45 ± 2 244 ± 11 2.6 ± 0.4 21± 1 66 ± 2 0 1 wt % + 300° C., 5 hr + 150 kGy 49 ± 2 303 ± 14 1.8 ± 0.122 ± 1 76 ± 2 0.1 wt % + 320° C., 5 hr + 150 kGy 47 ± 2 404 ± 21 3.6 ±0.4 24 ± 1 94 ± 3 0.2 wt % + 150-kGy 51 ± 3 278 ± 15 2.6 ± 0.2 21 ± 1 77± 2 0.2 wt % + 300° C., 5 hr + 150 kGy 48 ± 5 319 ± 24 2.0 ± 0.4 21 ± 187 ± 6 0.2 wt % + 320° C., 5 hr + 150 kGy 40 ± 1 369 ± 17 4.5 ± 0.3 24 ±1 96 ± 5

The IZOD impact strength of vitamin E-blended, high temperature meltedand irradiated UHMWPEs were all significantly higher than non-melted,irradiated UHMWPEs (Table 10). Most importantly, despite a severedecrease in cross-link density, vitamin. E-containing, high temperaturemelted, radiation cross-linked UHMWPEs had remarkably low wear (Table11). Therefore, these materials have improved fracture resistance andwear resistance compared to virgin irradiated and vitamin E-containingirradiated UHMWPEs. Due to the presence of the antioxidant, they arerendered oxidatively stable.

TABLE 11 Cross-link density and wear rate of vitamin E-containing, hightemperature melted, radiation cross-linked UHMWPE Cross-link densityWear rate (mol/m³) (mg/MC) 100-kGy irradiated 152 ± 5 −2.69 ± 0.80 0.1wt % + 150-kGy 164 ± 4 −1.96 ± 0.75 0.1 wt % + 300° C., 5 hr + 150 kGy140 ± 4 −1.69 ± 0.50 0.1 wt % + 320° C., 5 hr + 150 kGy  83 ± 2 −2.62 ±0.18 0.2 wt % + 150-kGy 148 ± 4 −2.62 ± 0.89 0.2 wt % + 300° C., 5 hr +150 kGy 129 ± 1 0.2 wt % + 320° C., 5 hr + 150 kGy  83 ± 2

Example 7. Chain Diffusion and Grain Boundary Profile of HighTemperature Melted UHMWPE

A puck of GUR1050 UHMWPE was high temperature melted in a convectionoven equipped with a nitrogen purge (LLD1-16N-3, Despatch Inc., MN) at300° C. for 5 hours and were cooled down under nitrogen purge to roomtemperature. It was freeze fractured in liquid nitrogen and coated withgold using a sputter coater. A puck of GUR1050 UHMWPE that had not beenhigh temperature melted was used as control.

The microscopy images were taken on a FBI-Phillips environmentalscanning electron microscope equipped with a backscatter electrondetector.

The grain boundaries of the high temperature melted sample (FIG. 39b )were much less discernable than the conventional slab compression moldedUHMWPE sample (FIG. 39a ). This suggested that there were diffusion ofthe polymer chains across the grain boundary.

Example 8. High Temperature Melting of Vitamin E-Blended and RadiationCross-Linked UHMWPEs

Vitamin E-blended UHMWPE (0.1 wt % and 0.2 wt %) was prepared by mixingGUR1050 UHMWPE powder with a 10 wt % isopropyl alcohol solution ofvitamin E and subsequently drying the powder at 60° C. Then the powderwas consolidated into pucks (10 cm diameter, 1 cm thickness) using alaboratory press (3895, Carver, Wabash, Ind.). The pucks were thenpackaged in vacuum and irradiated by electron-beam irradiation (Iotron,Vancouver, BC) to 150 kGy at 50 kGy/pass. After irradiation, they werehigh temperature melted in a convection oven equipped with a nitrogenpurge (LLD1-16N-3, Despatch Inc., MN) at 300° C. for 5 hours and werecooled down under nitrogen purge to room temperature.

Tensile testing was performed on dog-bones (Type V, ASTM D-638) stampedout of 3.2 mm-thick sections machined from high temperature meltedUHMWPEs. Testing was performed at 10 mm/min (MTS Insight, Eden Prairie,Minn.). Elongation to break (EAB) was determined by using a laserextensometer. Work to failure was determined as the area under theengineering stress-strain curves. The IZOD single-notch impact testswere done according to ASTM F648 (Orthoplastics, Lancashire, UK).Ultimate tensile strength (UTS) and elastic modulus (E) were alsomeasured.

Wear rates were determined by pin-on-disc wear testing on acustom-designed bidirectional wear tester (see Bragdon C R, O'Connor DO, Lowenstein J D, Jasty M, Biggs S A, Harris W H. A new pin-on-discwear testing method for simulating wear of polyethylene on cobalt-chromealloy in total hip arthroplasty. Journal of Arthroplasty 2001: 41(2):795-808). Testing was performed in undiluted, preserved bovine serum at2 Hz for 2 million cycles (MC) with gravimetric assessment of wear atapproximately every 500,000 cycles. Wear rate was determined as a linearregression of weight loss as a function of number of cycles from 0.5 to2 MC.

Crosslink density measurements of cross-linked UHMWPE (n=3 each) wereperformed on small samples (approximately 3×3×3 mm). The samples wereweighed before swelling in xylene at 130° C. and they were weighedimmediately after swelling in xylene. Therefore, the amount of xyleneuptake was determined gravimetrically, then converted to volumetricuptake by dividing by the density of xylene; 0.75 g/cc. By assuming thedensity of polyethylene to be approximately 0.99 g/cc, the volumetricswell ratio of crosslinked UHMWPE was then determined. The cross-linkdensity was calculated using the swell ratio as described previously(Muratoglu et al, Biomaterials 20:1463-1470 (1999)) and is reported asmol/m³.

Thin sections (150 μm-thick) were microtomed and analyzed using FourierTransform Infrared Spectroscopy (FTIR), A vinyl index was calculatedusing the area under 880-920 cm⁻¹ and normalizing it to the area under1895 cm⁻¹.

TABLE 12 Crystallinity and peak melting point of irradiated, hightemperature melted vitamin E-blended UHMWPEs. Crystallinity Peak meltingVinyl (%) point (° C.) index 0.1 wt % + 150-kGy 60 ± 0 139.4 0.1 wt % +300° C., 5 hr 55 ± 0 134.5 0.019 0.1 wt % + 150 kGy + 300° C., 5 hr 52 ±1 131.3 0.012 0.2 wt % + 150-kGy 60 ± 1 139.3 0.2 wt % + 300° C., 5 hr0.2 wt % + 150 kGy + 300° C., 5 hr 51 ± 1 131.1 0.012

TABLE 13 Tensile mechanical properties of irradiated, high temperaturemelted vitamin E-blended UHMWPEs. UTS (MPa) EAB (%) WF (kJ/m²) 0.1 wt% + 150-kGy 45 ± 2 244 ± 11 1344 ± 97  0.1 wt % + 300° C., 5 hr 0.1 wt% + 150 kGy + 300° C., 5 hr 43 ± 2 329 ± 16 1794 ± 160 0.2 wt % +150-kGy 51 ± 3 278 ± 15 1784 ± 174 0.2 wt % + 300° C., 5 hr 0.2 wt % +150 kGy + 300° C., 5 hr 48 ± 2 356 ± 9  2210 ± 138

TABLE 14 Cross-link density and wear of irradiated, high temperaturemelted vitamin E-blended UHMWPEs. Cross-link density (mol/m³) Wear rate(mg/MC) 0.1 wt % + 150-kGy 164 ± 4 −2.0 ± 0.8 0.1 wt % + 300° C., 5 hr —0.1 wt % + 150 kGy + 300° C., 5 hr 131 ± 3 −2.42 ± 0.46 0.1 wt % + 150kGy + 300° C., 12 hr  99 ± 1 −3.16 ± 0.97 0.2 wt % + 150-kGy 148 ± 4−2.62 ± 0.89 0.2 wt % + 300° C., 5 hr — 0.2 wt % + 150 kGy + 300° C., 5hr  119 ± 13

Example 9. High Temperature Melting of Vitamin E-Blended and RadiationCross-Linked UHMWPEs at Different Temperatures

Vitamin E-blended UHMWPE (0.1 wt % and 0.2 wt %) was prepared by mixingGUR1050 UHMWPE powder with a 10 wt % isopropyl alcohol solution ofvitamin E and subsequently drying the powder at 60° C. Then the powderwas consolidated into pucks (10 cm diameter, 1 cm thickness) using alaboratory press (3895, Carver, Wabash, Ind.). The pucks were thenpackaged in vacuum and irradiated by electron-beam irradiation (Iotron,Vancouver, BC) to 150 kGy at 50 kGy/pass. After irradiation, they werehigh temperature melted in a convection oven equipped with a nitrogenpurge (LLD1-16N-3, Despatch Inc., MN) at 280° C. for 5 hours or at 300°C. for 1, 5 or 12 hours and were cooled down under nitrogen purge toroom temperature.

Tensile testing was performed on dog-bones (Type V, ASTM D-638) stampedout of 3.2 mm-thick sections machined from high temperature meltedUHMWPEs. Testing was performed at 10 mm/min (MTS Insight, Eden Prairie,Minn.). Elongation to break (EAB) was determined by using a laserextensometer. Work to failure was determined as the area under theengineering stress-strain curves. The IZOD single-notch impact testswere done according to ASTM F648 (Orthoplastics, Lancashire, UK).Ultimate tensile strength (UTS) and elastic modulus (E) were alsomeasured.

Wear rates were determined by pin-on-disc wear testing on acustom-designed bidirectional wear tester (see Bragdon C R, O'Connor DO, Lowenstein J D, Jasty M, Biggs S A, Harris W H. A new pin-on-discwear testing method for simulating wear of polyethylene on cobalt-chromealloy in total hip arthroplasty. Journal of Arthroplasty 2001: 41(2):795-808). Testing was performed in undiluted, preserved bovine serum at2 Hz for 2 million cycles (MC) with gravimetric assessment of wear atapproximately every 500,000 cycles. Wear rate was determined as a linearregression of weight loss as a function of number of cycles from 0.5 to2 MC.

High temperature melting of vitamin E-blended UHMWPE after radiationcross-linking resulted in decreased cross-link density as a function ofincreasing duration at the same temperature (Table 15). In addition, theelongation to break and work to failure increased with duration whileultimate tensile strength was largely not affected. Increasing thetemperature of the high temperature melting process at the same durationdecreased cross-link density, increased elongation at break and work tofailure while did not affect ultimate tensile strength significantly.

TABLE 15 Cross-link density and tensile mechanical properties of vitaminE-blended, radiation cross-linked and subsequently high temperaturemelted UHMWPEs. Cross-link density (mol/m³) UTS (MPa) EAB (%) WF (kJ/m²)0.1 wt % + 150 kGy 164 ± 4 45 ± 2 244 ± 11 1344 ± 97  0.1 wt % + 150kGy + 280° C., 5 hr 156 ± 8 43 ± 4 290 ± 12 1578 ± 216 0.1 wt % + 150kGy + 300° C., 1 hr 152 ± 2 44 ± 2 302 ± 12 1669 ± 122 0.1 wt % + 150kGy + 300° C., 5 hr 131 ± 3 43 ± 2 329 ± 16 1794 ± 160 0.1 wt % + 150kGy + 300° C., 12 hr  99 ± 1 48 ± 3 387 ± 15 2401 ± 267 0.2 wt % + 150kGy 148 ± 4 51 ± 3 278 ± 15 1784 ± 174 0.2 wt % + 150 kGy + 280° C., 5hr 132 ± 2  45 ± 17 321 ± 22 1883 ± 484 0.2 wt % + 150 kGy + 300° C., 1hr 130 ± 2 46 ± 2 326 ± 8  1902 ± 143 0.2 wt % + 150 kGy + 300° C., 5 hr119 ± 3 46 ± 3 356 ± 9  2210 ± 138 0.2 wt % + 150 kGy + 300° C., 12 hr101 ± 5 45 ± 5 381 ± 16 2149 ± 377

Example 10. Wear as a Function of Cross-Link Density in High TemperatureMelted UHMWPEs

Vitamin E-blended UHMWPE (0.1 wt %) was prepared by mixing GUR1050UHMWPE powder with a 10 wt % isopropyl alcohol solution of vitamin E andsubsequently drying the powder at 60° C. Then the powder wasconsolidated into pucks (10 cm diameter, 1 cm thickness) using alaboratory press (3895, Carver, Wabash, Ind.). The pucks were then hightemperature melted in a convection oven equipped with a nitrogen purge(LLD1-16N-3, Despatch Inc., MN) at 300° C. 5 hours and were cooled downunder nitrogen purge to room temperature. Then they were packaged invacuum and irradiated by electron-beam irradiation (Iotron, Vancouver,BC) to 150 kGy at 50 kGy/pass. Virgin UHMWPE consolidated withoutvitamin E was used as control.

Cylindrical pins (n=3 each, 9 mm diameter, 13 mm length) were machinedfrom high temperature melted and irradiated UHMWPEs. Wear rates weredetermined by pin-on-disc wear testing on a custom-designedbidirectional wear tester (see Bragdon C R, O'Connor D O, Lowenstein JD, Jasty M, Biggs S A, Harris W H. A new pin-on-disc wear testing methodfor simulating wear of polyethylene on cobalt-chrome alloy in total hiparthroplasty. Journal of Arthroplasty 2001: 41(2): 795-808). Testing wasperformed in undiluted preserved bovine serum at 2 Hz for approximately1.2 million cycles (MC) with gravimetric assessment of wear atapproximately every 250,000 cycles. Wear rate was determined as a linearregression of weight loss as a function of number of cycles from 0.5 to1.2 MC.

The other samples in Table 16 and FIG. 40 were irradiated asconsolidated blocks and melted in a vacuum oven at the designatedtemperature in partial vacuum/argon. They were tested similarly at 2 Hzfor 2 MC with gravimetric assessment at every 500,000 cycles. Wear ratewas determined as a linear regression of weight loss as a function ofnumber of cycles from 0.5 to 2 MC.

TABLE 16 Wear rate of samples shown in FIG. 40. Wear rate (mg/MC)Virgin, 300° C. 5 hours + 150 kGy −1.4 Virgin, 320° C. 5 hours + 150 kGy−1.9 0.1 wt % + 300° C. 5 hours + 150 kGy −1.7 0.1 wt % + 320° C. 5hours + 150 IcGy −2.6 0.1 wt % + 150 kGy −2.0 25 kGy −6.4 Unirradiatedvirgin −10.1 Unirradiated 0.1 wt % vitamin E-blended −7.8 65 kGy gammairradiated and melted at 200° C. −2.9 65 kGy e-beam irradiated andmelted at 170° C. −2.2 100 kGy gamma irradiated and melted at 200° C.−0.9 100 kGy e-beam irradiated and melted at 150° C. −1.3

The high temperature treated samples showed wear rates of less than −3.5mg/MC for cross-link density of approximately less than 140 mol/m³,while irradiated and irradiated and melted UHMWPEs required at leastthis much cross-linking.

It is clearly shown in FIG. 40 that samples which were treated by hightemperature melting prior to irradiation had lower wear rates despitelower cross-link density. For example, at a cross-link density of about90 mol/m³, simply irradiated UHMWPE had a wear rate of around −6 mg/MCwhile high temperature melted and irradiated UHMWPE had a wear rate ofapproximately −2.0 mg/MC. From another data point, for example, a wearrate of less than 3.5 mg/MC for cross-link density lower than 140 mol/m3is achieved by high temperature melting and subsequently irradiating theUHMWPE, a much higher wear resistance, which is not achievable withradiation cross-linked or cross-linked and melted UHMWPE.

Example 11. High Temperature Melting of Irradiated and Melted UHMWPE

A puck of GUR 1020 or GUR1050 UHMWPE is irradiated to 25, 50, 100, 150,200, and 500 kGy by ionizing radiation. Similarly, GUR1020 or GUR1050blended with 0.05, 0.1, 0.2, 0.3, 0.5, 1.0, 2.0 and 5.0 wt % vitamin Eis irradiated to 25, 50, 100, 150, 200 and 500 kGy by ionizingradiation. The samples are further melted at 170° C. until transparentin air or in vacuum, then they are cooled down to about roomtemperature. Further, they are melted at 280, 300, 320, and 340° C. forabout 5 hours in inert gas, then cooled down under inert gas to aboutroom temperature. In this manner, the wear resistance and toughness ofirradiated and melted UHMWPEs is increased.

Example 12. Warm and Cold Irradiation of High Temperature Melted,Radiation Cross-Linked UHMWPEs

Vitamin E-blended UHMWPE (0.1 wt %, 0.2 wt %, 1 wt %, 2 wt %, 5 wt %)are prepared by mixing GUR1050 UHMWPE powder with a 10 wt % isopropylalcohol solution of vitamin E and subsequently drying the powder at 60°C. Then the powder is consolidated into pucks (10 cm diameter, 1 cmthickness) using a laboratory press (3895, Carver, Wabash, Ind.). Thepucks are then packaged in vacuum and irradiated by electron-beamirradiation (Iotron, Vancouver, BC) to 25, 50, 100, 150, 200 and 500 kGyat 50 kGy/pass starting at room temperature (cold irradiated).Alternatively, they are pre-heated in a convection oven at approximately120° C., then warm irradiated. After irradiation, they are hightemperature melted in a convection oven equipped with a nitrogen purge(LLD1-16N-3, Despatch Inc., MN) at 300° C. for 1, 5 or 12 hours and werecooled down under nitrogen purge to room temperature.

Example 13. Warm and Cold Irradiation of Radiation Cross-Linked, HighTemperature Melted UHMWPEs

Vitamin E-blended UHMWPE (0.1 wt %, 0.2 wt %, 1 wt %, 2 wt %, 5 wt %)are prepared by mixing GUR1050 UHMWPE powder with a 10 wt % isopropylalcohol solution of vitamin E and subsequently drying the powder at 60°C. Then the powder is consolidated into pucks (10 cm diameter, 1 cmthickness) using a laboratory press (3895, Carver, Wabash, Ind.). Thepucks are then high temperature melted in a convection oven equippedwith a nitrogen purge (LLD1-16N-3, Despatch Inc., MN) at 300° C. for 1,5 or 12 hours and were cooled down under nitrogen purge to roomtemperature. Then they are packaged in vacuum and irradiated byelectron-beam irradiation (Intron, Vancouver, BC) to 25, 50, 100, 150,200 and 500 kGy at 50 kGy/pass starting at room temperature (coldirradiated). Alternatively, they are pre-heated in a convection oven atapproximately 120° C., then warm irradiated.

Example 14. The Effect of Irganox® 1010, Irganox® 1076 and Irganox® 1035on the Cross-Link Density of UHMWPE

Consolidated blends of GUR1050 UHMWPE were made with Irganoxes usingsolvent (IPA) blending of Irganox® 1010, Irganox® 1076 and Irganox® 1035with UHMWPE resin powder, evaporating the solvent and compressionmolding the blended powder in a press. Blended powder was either made atthe desired concentration or made at a higher concentration ofantioxidant and diluted down with UHMWPE powder. In this manner, UHMWPEcontaining 0.01 wt %, 0.02 wt %, 0.05 wt %, 0.1 wt %, 0.2 wt %, 0.3 wt%, 0.5 wt % and 1.0 wt % Irganox® 1010, Irganox® 1076, and Irganox® 1035were made.

Compression molded pucks (diameter ˜10 cm, thickness ˜1 cm) wereirradiated to 50, 100, 150 and 200 kGy using electron beam irradiation.

Cross-link density was measured by swelling ˜3 mm cubes in xylene at130° C. for 2 hours and immediately sealing in pre-weighed vials forweighing. A volumetric expansion ratio was determined by converting theweight swelling ratio using the density of the dry polymer (0.95 g/cm³)and of xylene at 130° C. (0.75 g/cm³). Cross-link density (in mol/m³)was calculated as described using the following equation:

$v_{d} = {{- \left( \frac{{\ln\left( {1 - \frac{1}{\rho}} \right)} + \frac{1}{\rho} + {\frac{1}{\rho^{2}}\left( {0.33 + \frac{0.55}{\rho}} \right)}}{136 \times \left( {\frac{1}{\rho^{\frac{1}{3}}} - \frac{1}{2\rho}} \right)} \right)} \times 1000}$

It was observed that increasing antioxidant concentration decreasedcross-linking in UHMWPE and thus, the radiation dose required to obtain260 mol/m³ of cross-link density (equivalent to that of 100-kGyirradiated virgin UHMWPE) in antioxidant-blended UHMWPEs increased withincreasing antioxidant concentration (FIGS. 41a-c and Table 17).

TABLE 17 Radiation doses required to obtain a crosslink density of 0.260mol/dm³ in antioxidant blended GUR1050 UHMWPEs for different singleantioxidant blends. Irganox ®1010 Irganox ®1035 Irganox ®1076 Vitamin E0.01 110 112 96 110 0.02 111 115 108 110 0.05 122 144 127 118 0.1 136168 142 123 0.2 199 293 176 150 0.3 199 330 251 189 0.5 228 464 321 2451.0 230 627 651 540

This result also implies that by having different spatial concentrationof these Irganoxes and mixtures of these antioxidants with each other inUHMWPE, the cross-link density distribution can be controlled andmanipulated.

Example 15. Surface Cross-Linking with Irganox® 1010

A consolidated puck containing 1 wt % Irganox® 1010-blended GUR1050UHMWPE on one side and virgin UHMWPE on the other side was prepared bylayering of 1 wt % Irganox® 1010-blended UHMWPE powder and virgin UHMWPEpowder followed by compression molding (FIG. 42a ).

To determine the spatial variation of the antioxidant concentrationthroughout the samples, 150 μm-thick sections that were microtomed froman inner surface (FIG. 43; n=3 each) were analyzed using FourierTransform Infrared Spectroscopy (FTIR). An Irganox® index was calculatedas a function of depth away from the surface as the ratio of the areasunder 1223 cm⁻¹-1245 cm⁻¹ to the absorbance over 1875 cm⁻¹-1905 cm⁻¹.

The Irganox® concentration in the sample was constant for part of thesample after which it decreased gradually to undetectable limits wherethe 1 wt % Irganox® 1010-blended UHMWPE had been consolidated with thevirgin UHMWPE (FIG. 43b ). When this material is irradiated, the surfacewill be highly cross-linked and the bulk will have lower cross-linkdensity.

Example 16. Antioxidant Bleeding During Layered Molding

A consolidated puck containing 1 wt % Irganox® 1010-blended UHMWPE onone side and virgin UHMWPE on the other side was prepared by layering of1 wt % Irganox® 1010-blended UHMWPE powder and virgin UHMWPE powderfollowed by compression molding (FIG. 42a ). A similar puck containing 1wt % vitamin E-blended UHMWPE on one side and virgin UHMWPE on the otherside was also prepared.

To determine the spatial variation of the antioxidant concentrationthroughout the samples, 150 μm-thick sections were microtomed from aninner surface (FIG. 43; n=3 each) were analyzed using FTIR. An Irganox®index were calculated as a function of depth away from the surface asthe ratio of the areas under 1223 cm⁻¹-1245 cm⁻¹ to the absorbance over1875 cm⁻¹-1905 cm⁻¹. A vitamin E index was calculated as the ratio ofthe areas under 1245 cm⁻¹-1275 cm⁻¹ to the absorbance over 1875cm⁻¹-1905 cm⁻¹.

The gradient interface width of the Irganox® 1010-virgin layered puckwas approximately 3 mm (with a low threshold of Irganox® index of 0.02)whereas the gradient width of the vitamin E-virgin layered puck wasapproximately 2 mm (FIG. 44).

Example 17. Surface Cross-Linking with More than One Antioxidant

A consolidated puck containing 1 wt % vitamin E blended UHMWPE on oneside and 0.1 wt % Irganox® 1010 blended UHMWPE on the other side wasprepared by layering of 1 wt % vitamin E-blended UHMWPE powder and 0.1wt % Irganox®-blended UHMWPE powder followed by compression molding(FIG. 42a ).

To determine the spatial variation of the antioxidant concentrationthroughout the samples, 150 μm-thick sections that were microtomed froman inner surface (FIG. 43; n=3 each) were analyzed using FTIR. Irganox®index were calculated as a function of depth away from the surface asthe ratio of the areas under 1223 cm⁻¹-1245 cm⁻¹ to the absorbance over1875 cm⁻¹-1905 cm⁻¹. Vitamin E index was calculated as the ratio of theareas under 1245 cm⁻¹-1275 cm⁻¹ to the absorbance over 1875 cm⁻¹-1905cm⁻¹.

Vitamin E and Irganox® 1010 profiles showed that one side of the puck(˜7-10 mm) contained only Irganox® 1010 and the other side (0-5.8 mm)contained only vitamin E (FIG. 45). The gradient interface containingboth antioxidants was approximately 1.2 mm. When this puck isirradiated, it has different cross-link density in the bulk and surface.

Example 18. Preferential Surface Cross-Linking by Machining

A UHMWPE puck containing a spatial distribution of high and lowconcentrations of at least one antioxidant is made by layered molding asdescribed in Example 15 and FIG. 42a . Antioxidants can be chosen frombut not limited to glutathione, lipoic acid, vitamins such as ascorbicacid (vitamin C), vitamin B, vitamin D, vitamin-E, tocopherols(synthetic or natural, alpha-, gamma-, delta-), acetate vitamin esters,water soluble tocopherol derivatives, tocotrienols, water solubletocotrienol derivatives; melatonin, carotenoids including variouscarotenes, lutein, pycnogenol, glycosides, trehalose, polyphenols andflavonoids, quercetin, lycopene, lutein, selenium, nitric oxide,curcuminoids, 2-hydroxytetronic acid; cannabinoids, syntheticantioxidants such as tertiary butyl hydroquinone, 6-amino-3-pyrodinoles,butylated hydroxyanisole, butylated hydroxytoluene, ethoxyquin, tannins,propyl gallate, other gallates, Aquanox family; Irganox® and Irganox® Bfamilies including Irganox® 1010, Irganox® 1076, Irganox© 1035, Irganox®1330; Irgafos® family; phenolic compounds with different chain lengths,and different number of OH groups; enzymes with antioxidant propertiessuch as superoxide dismutase, herbal or plant extracts with antioxidantproperties such as St. John's Wort, green tea extract, grape seedextract, rosemary, oregano extract, mixtures, derivatives, analogues orconjugated forms of these. They can be primary antioxidants withreactive OH or NH groups such as hindered phenols or secondary aromaticamines, they can be secondary antioxidants such as organophosphoruscompounds or thiosynergists, they can be multifunctional antioxidants,hydroxylamines, or carbon centered radical scavengers such as lactonesor acrylated bis-phenols. The antioxidants can be selected individuallyor used in any combination. Further, antioxidants can be used incombination with other compounds such as hydroperoxide decomposers.

The layered molded puck has two layers of containing UHMWPE wherein oneside will be more crosslinked than the other after irradiation. Thesurface of an implant or preform fabricated from this layered moldedmaterial can be further manipulated by machining (FIG. 46). For example,the surface is machined such that the articular surface is concave andthe outside part of the surface is machined down to the UHMWPEcontaining high antioxidant concentration (FIG. 46b ). Alternatively,the surface can have a contour after machining such that part of thesurface contains more than another part (FIGS. 46a-46g ). Such surfacesare then radiation crosslinked, yielding an implant or preform surfacewith preferentially crosslinked regions.

Example 19. Preferential Crosslinking by Using Different MoldingConfigurations

A UHMWPE puck containing a spatial distribution of high and lowconcentrations of at least one antioxidant is made by layered molding byusing layering in different configurations. For example, there can bemore than two layers having different concentrations of at least oneantioxidant (FIG. 47a ).

Alternatively, the blends are layered in such a way to allow for highconcentration regions within the low concentration regions (FIGS. 47band 47c ). The mold is topped with a low concentration layer which ismachined away as desired.

Example 20. Preferential Surface Crosslinking by Masking

A method of creating a spatial distribution of antioxidant concentrationthrough UHMWPE is to extract some antioxidant from a compression moldedantioxidant blend of UHMWPE. In this way, the antioxidant concentrationis lowered at the surface of the blended piece, and irradiation of sucha piece yields a highly cross-linked surface and a less cross-linkedbulk region. In another method, the surface is crosslinkedpreferentially by using masking of parts of the surface duringextraction, followed by irradiation (FIG. 48). The masking will servethe purpose of preventing antioxidant extraction from masked regions andlimit the extraction to unmasked regions. This method will allow one toachieve an implant with crosslinking only in the regions where it isdesired; for instance on the articular surfaces but not where thelocking mechanisms are located.

Example 21. Irganox® Blends (Powder Vs. Solution Blends)

Irganox® 1010 was blended with UHMWPE powder using two methods: solventblending and dry blending. In the solvent blend, the Irganox® 1010 wasdissolved first in isopropyl alcohol (IPA) at room temperature or at aslightly elevated temperature around 40° C., then the solution was mixedwith UHMWPE powder at the desired concentration. The solvent was driedoff in a vacuum oven at 60° C. for at least one week. In the powderblend, Irganox® powder was mixed directly with UHMWPE powder at thedesired concentration.

To determine the spatial variation of the antioxidant concentrationthroughout the samples, 150 μm-thick sections that were microtomed froman inner surface (FIG. 43; n=3 each) were analyzed using FTIR. Irganox®index were calculated as a function of depth away from the surface asthe ratio of the areas under 1223 cm⁻¹-1245 cm⁻¹ to the absorbance over1875 cm⁻¹-1905 cm⁻¹.

The concentration profile of Irganox® 1010 through the compressionmolded UHMWPE pucks fabricated from solvent blend and powder blend ofIrganox® 1010 with UHMWPE before annealing are shown in FIG. 49. Thesolvent blend was more homogenous after molding. But, the concentrationprofile of the powder blend was also homogenized by annealing the puckat 130° C. for 64 hours (FIG. 49).

Example 22. Oxidative Stability of Irradiated Irganox® 1010 Blends ofUHMWPE

UHMWPE pucks containing a uniform concentration of 0.1 wt % Irganox®1010 were prepared by solvent blending Irganox® 1010 with UHMWPE powder(Example 21) and compression molding (FIG. 42a ). Pucks were useduntreated or were irradiated to 150 kGy for cross-linking. Control wasvirgin UHMWPE irradiated to 150 kGy.

Two accelerated aging methods were used: 14 days at 70° C. under 5 atm.of oxygen (ASTM F2003) and 14 days at 70° C. under 5 atm. of oxygenafter squalene doping. Squalene is an unsaturated lipid, which initiatedsevere oxidation in irradiated and melted UHMWPE. Cubes (1 cm) weremachined from Irganox® 1010 blended pucks and irradiated blended pucks.Squalene doping was done in pre-heated squalene at 120° C. for 2 hoursin air.

After accelerated aging, the 150 μm-thick sections were microtomed froman inner surface (FIG. 43; n=3 each). These sections were boiled inhexane overnight and then dried in vacuum at room temperature for 24hours. They were then analyzed by FTIR. An oxidation index wascalculated as a function of depth away from the surface as the ratio ofthe areas under 1680 cm⁻¹-1780 cm⁻¹ to the absorbance over 1370 cm⁻¹ perASTM F2003.

After accelerated aging both with (FIG. 50b ) and without lipids (FIG.50a ), irradiated virgin UHMWPE oxidized heavily, whereas irradiatedIrganox® 1010 blends showed substantially lower oxidation. Thenon-irradiated Irganox® 1010 blends showed no detectable oxidation,those that were irradiated showed very small oxidation near the surface.

These results showed that Irganox® 1010 increased the oxidativestability of UHMWPE substantially after irradiation.

Example 23. Wear Resistance of Irradiated Irganox® 1010 Blends of UHMWPE

The wear rate (mg/million cycles) of irradiated blends of Irganox® 1010with UHMWPE was measured using a bidirectional pin-on-disc wear tester(AMTI Orthopod, Watertown. Mass.). Cylindrical pins (diameter 9 mm,length 13 mm) were articulated against medical grade polished CoCr discsin a rectangular pattern (R_(a)=0.03-0.05 μm) at 2 Hz in bovine serum atroom temperature, Wear was assessed by gravimetric measurements at 0.5MC and at every subsequent 0.15 million-cycle (MC) and the wear rate wasdetermined as the linear regression of wear vs. number of cycles from0.5 MC to the end of the test (1.2 MC).

TABLE 18 POD wear rates of irradiated Irganox ® 1010 blends of UHMWPE.Material Wear rate (mg/MC) Virgin + 150 kGy  −0.8 ± 0.2 0.1 wt % solventblend of Irganox ® 1010 −13.6 ± 1.1 0.1 wt % solvent blend of Irganox ®1010 +  −0.5 ± 0.0 150 kGy 0.1 wt % powder blend of Irganox ® 1010 + −0.9 ± 0.4 150 kGy

The wear rates of irradiated 0.1 wt % Irganox® 1010 blends of UHMWPEwere comparable to or less than that of 150 kGy irradiated virgin UHMWPE(Table 17).

Example 24. Extraction of Irganox® with Hexane

One UHMWPE puck each containing a uniform concentration of Irganox® 1010(0.1 wt %) was prepared by solvent blending or dry powder blendingIrganox® 1010 with UHMWPE powder (Example 21) and compression molding(FIG. 42a ).

To determine the spatial variation of the antioxidant concentrationthroughout the samples, 150 μm-thick sections were microtomed from aninner surface (FIG. 43; n=3 each) were analyzed using FTIR. Irganox®index were calculated as a function of depth away from the surface asthe ratio of the areas under 1223 cm⁻¹-1245 cm⁻¹ to the absorbance over1875 cm⁻¹-1905 cm⁻¹.

Microtomed sections were boiled in hexane overnight (˜16 hours) and weredried in vacuum at room temperature for 24 hours. Irganox® content wasmeasured before and after hexane extraction as a function of depth awayfrom the surface of the molded puck.

The concentration profiles after hexane extraction in both samples wasclose to undetectable (FIG. 51), suggesting efficient extraction ofIrganox® from the UHMWPE.

Example 25. Annealing for Redistribution of Antioxidants

A UHMWPE puck with high and low concentrations of Irganox® 1010 is madeby layering blend powder in any configuration, for example as describedin Example 6. Or, a UHMWPE puck with a high concentration of vitamin Ein the bulk and a low concentration of an Irganox® antioxidant is madeby layering blend powder. Then, it is radiation crosslinked. Afterradiation cross-linking it is annealed below, at or above the meltingtemperature at 100, 110, 120, 130, 140, 150, 170, or 300° C. for 1 hour,2 hours, 4 hours, 8 hours, 24 hours, 36 hours, 64 hours or 300 hours or1000 hours. In this manner, the antioxidant in the regions containinghigh antioxidant concentration is redistributed to the regions with lowantioxidant concentration. Annealing is alternatively done in asupercritical carbon dioxide environment.

Example 26. Blending with More than One Antioxidant

A consolidated blend of GUR1050 UHMWPE was made using solvent (IPA)blending of Irganox® 1010 and vitamin E with UHMWPE resin powder,evaporating the solvent and compression molding the blended powder in apress. Blended powder was made containing 0.1 wt % of each antioxidant.

Compression molded pucks (diameter ˜10 cm, thickness ˜1 cm) wereirradiated to 50, 100, 150 and 200 kGy using electron beam irradiation.

Cross-link density was measured and calculated as described in Example14 and are shown in FIG. 52.

Example 27. Blending with Vitamin E

Consolidated blends of GUR1050 UHMWPE were made with vitamin E usingsolvent (IPA) blending of vitamin E with UHMWPE resin powder,evaporating the solvent and compression molding the blended powder in apress. Blended powder was either made at the desired concentration ormade at a higher concentration of antioxidant and diluted down withUHMWPE powder. In this manner, UHMWPE containing 0.01 wt %, 0.02 wt %,0.05 wt %, 0.1 wt %, 0.2 wt %, 0.3 wt %, 0.5 wt % and 1.0 wt % vitamin Ewere made.

Compression molded pucks (diameter ˜10 cm, thickness ˜1 cm) wereirradiated to 50, 100, 150 and 200 kGy using electron beam irradiation.Cross-link density was measured and calculated as described in Example14.

It was observed that increasing antioxidant concentration decreasedcross-linking in UHMWPE and thus, the radiation close required to obtain260 mol/m³ of cross-link density (equivalent to that of 100-kGyirradiated virgin UHMWPE) in antioxidant-blended UHMWPEs increased withincreasing antioxidant concentration (FIG. 53).

Example 28. Oxidative Stability of Irradiated Antioxidant Blends

UHMWPE pucks containing a uniform concentration of 0.01 wt %, 0.02 wt %,0.05 wt % and 0.1 wt % Irganox® 1010 were prepared by solvent blendingIrganox® 1010 with UHMWPE powder (Example 21) and compression molding(FIG. 42a ). UHMWPE pucks containing a uniform concentration of 0.01 wt%, 0.02 wt %, 0.05 wt %, 0.1 wt %, 0.2 wt %, 0.3 wt % and 0.5 wt %vitamin E were prepared by solvent blending vitamin E with UHMWPE powder(Example 27) and compression molding (FIG. 42a ). Pucks were irradiatedto different doses to achieve 0.260 mol/dm³ of crosslink density (Table17). Control was virgin UHMWPE irradiated to 150 kGy.

A severe accelerated aging method was used: 14 days at 70° C. under 5atm. of oxygen after squalene doping. Squalene is an unsaturated lipid,which initiated severe oxidation in irradiated and melted UHMWPE. Cubes(1 cm) were machined from blended pucks and irradiated blended pucks.Squalene doping was done in pre-heated squalene at 120° C. for 2 hoursin air.

After accelerated aging, the 150 μm-thick sections were microtomed froman inner surface (FIG. 43; n=3 each). These sections were boiled inhexane overnight and then dried in vacuum at room temperature for 24hours. They were then analyzed by FTIR. An oxidation index wascalculated as a function of depth away from the surface as the ratio ofthe areas under 1680 cm⁻¹-1780 cm⁻¹ to the absorbance over 1370 cm⁻¹ perASTM F2003.

After squalene challenge and bomb aging under elevated oxygen partialpressure, irradiated vitamin B blends containing less than 0.1 wt %vitamin E oxidized (FIG. 54). In contrast, under the same conditions,irradiated Irganox® 1010 blends containing less than 0.05 wt % Irganox®1010 oxidized (FIG. 55). Therefore, Irganox® 1010 appeared to be moreeffective towards oxidation induced by squalene during accelerated agingthan vitamin E.

Example 29. Diffusion and Homogenization of Irganox® in UHMWPE

Virgin UHMWPE was machined into blocks (1 cm³). Irganox® 1010 waspre-heated to 130° C. in a convection oven. Cubes were doped in thispre-heated Irganox® 1010 for 6 hours at 130° C. The cubes were thenremoved from Irganox® 1010 and the excess antioxidant on the surface waswiped off. Then they were placed in homogenization for 64 hours at 130°C. To determine the spatial variation of the antioxidant concentrationthroughout the samples, 150 μm-thick sections were microtomed from aninner surface (FIG. 43; n=3 each) were analyzed using FTIR. Irganox®index were calculated as a function of depth away from the surface asthe ratio of the areas under 1223 cm⁻¹-1245 cm⁻¹ to the absorbance over1875 cm⁻¹-1905 cm⁻¹.

A more uniform Irganox® 1010 profile was obtained by using doping ofUHMWPE in Irganox® 1010 followed by homogenization of the high surfaceconcentration obtained by doping (FIG. 56). The obtained concentrationwas similar to that obtained by solvent blending of Irganox® 1010 inUHMWPE and compression molding of the blend (FIG. 57).

Example 30. Mechanical Properties of Surface Crosslinked UHMWPE

GUR1050 UHMWPE pucks were prepared as described in FIG. 42a by layeredcompression molding of 1 or 2 wt % vitamin E-blended UHMWPE in one layerand 0.05 wt % vitamin E-blended UHMWPE resin powder in the other layer.Blending of the antioxidant into the powder was made by dissolving inIPA, mixing the solution with UHMWPE powder, and evaporating the solventby vacuum drying at 60° C. The thickness of the layer molded with lowvitamin E concentration was approximately 2 mm and the rest containedthe higher concentration of vitamin E.

One puck each (10 cm diameter, ˜6.4 mm thickness) was vacuum packagedand irradiated to 75, 100 and 150 kGy by electron beam irradiation (2.5MeV generator, MIT) at 25 kGy/pass. The irradiated pucks were machinedinto IZOD impact testing coupons (ASTM F648) without machining away thesurface layer and notched and tested according to ASTM F648 atOrthoplastics Ltd, UK.

TABLE 19 Impact strength of surface crosslinked UHMWPEs containing 1 wt% and 0.05 wt % vitamin E. Radiation IZOD Impact strength (kJ/m²) Dose(kGy) Surface crosslinked No surface crosslinking 75 109 ± 3 124 ± 2 100 97 ± 3 118 ± 1 150  83 ± 4  93 ± 4

TABLE 20 Impact strength of surface crosslinked UHMWPEs containing 2 wt% and 0.05 wt % vitamin E. Radiation IZOD Impact strength (kJ/m²) Dose(kGy) Surface crosslinked No surface crosslinking 75 113 ± 3 130 ± 1

The IZOD impact strength of 100-key irradiated virgin UHMWPE was 72±2kJ/m² and that of unirradiated UHMWPE was 127±8 kJ/m². The IZOD impactstrength of surface crosslinked UHMWPE containing a surface of 30% ofthe entire thickness was 10-20% less than the 1 or 2 wt % vitamin Eblended and irradiated UHMWPE without a crosslinked surface (Tables 19and 20). In addition, the impact strength of these UHMWPEs was 15 to 57%higher than that of 100-key irradiated UHMWPE.

To elucidate the thickness effect on the surface crosslinked layer onthe mechanical properties on the material, 3 UHMWPE pucks were preparedby layering and compression molding 1, 2 or 3 mm of 0.05 wt % vitamin Eblended GUR1050 UHMWPE powder with 1 wt % vitamin E blended UHMWPEpowder into 6.4 mm-thick sample. The pucks were then vacuum packaged andirradiated to 150 kGy. IZOD testing was done as described above. Theresults are shown in FIG. 58. The impact strength decreased withincreasing thickness of the highly crosslinked layer irradiated in thepresence of a lower vitamin E concentration.

Example 31. Homogenization of Antioxidants after Surface Crosslinking

GUR1050 UHMWPE pucks were prepared as described in FIG. 42a by layeredcompression molding of 1 wt % vitamin E-blended UHMWPE powder in onelayer and 0.05 wt % vitamin E-blended UHMWPE resin powder in the otherlayer. Blending of the antioxidant into the powder was made bydissolving in IPA, mixing the solution with UHMWPE powder, andevaporating the solvent by vacuum drying at 60° C. The thickness of thelayer molded with low vitamin E concentration was approximately 2 mm andthe rest contained the higher concentration of vitamin E.

One puck each (10 cm diameter, ˜6.4 mm thickness) was vacuum packagedand irradiated to 75,100 and 150 kGy by electron beam irradiation (2.5MeV generator, MIT) at 25 kGy/pass. After irradiation, the pucks weremachined into 1 cm by 1 cm by 6.4 mm blocks. One block each was annealedin argon at 135° C. for 16, 40, 64, 88 and 185 hrs. The vitamin Eprofiles were determined by FTIR spectroscopy before and afterannealing.

To determine the spatial variation of the antioxidant concentrationthroughout the samples, 150 μm-thick sections were microtomed from aninner surface (FIG. 43; n=3 each) were analyzed using FTIR. Vitamin Eindex was calculated as the ratio of the areas under 1245 cm⁻¹-1275 cm⁻¹to the absorbance over 1875 cm⁻¹-1905 cm⁻¹.

FIGS. 59a-b show the vitamin E profiles of homogenized surfacecrosslinked UHMWPE containing 1 wt % and 0.05 wt % vitamin E blends ofUHMWPE irradiated to 100 kGy (59 a) and 150 kGy (59 b). Homogenizationwas done after irradiation in argon at 135° C. for 16-185 hours. Thevitamin E index on the surface crosslinked side, which was undetectablebefore homogenization increased substantially (FIGS. 59a-b ). Thus, theoxidation resistance of this side increases as well.

Example 32. Homogenization of Surface Crosslinked UHMWPE in aSupercritical Medium

GUR1050 UHMWPE pucks are prepared as described in FIG. 42a by layeredcompression molding of 1 wt % vitamin E-blended UHMWPE in one layer and0.05 wt % vitamin E-blended UHMWPE resin powder in the other layer.Blending of the antioxidant into the powder is made by dissolving inIPA, mixing the solution with UHMWPE powder, and evaporating the solventby vacuum drying at 60° C. The thickness of the layer molded with lowvitamin E concentration is approximately 2 mm and the rest contains thehigher concentration of vitamin E.

One puck each (10 cm diameter, ˜6.4 mm thickness) is vacuum packaged andirradiated to 50, 75, 100, 150, 200, 250, 300, 350, 400 kGy by electronbeam irradiation (2.5 MeV generator, MIT) at 25 kGy/pass. Afterirradiation, the pucks are annealed in inert gas or supercritical carbondioxide at 45, 50, 60, 80, 100, 120, 130, 135, 150, 180, 200, 250, 280,300, 320° C. for 16, 40, 64, 88, 185 or 1000 hrs.

Example 33. Diffusion of Antioxidant in Surface Crosslinked UHMWPE

GUR1050 UHMWPE pucks are prepared as described in FIG. 42a by layeredcompression molding of 1 wt % vitamin E-blended UHMWPE in one layer and0.05 wt % vitamin E-blended UHMWPE resin powder in the other layer.Blending of the antioxidant into the powder is made by dissolving asolvent (such as an alcohol or alcohol mixture such as IPA, ethanol,methanol), mixing the solution with UHMWPE powder, and evaporating thesolvent by vacuum drying at 60° C. The thickness of the layer moldedwith low antioxidant concentration is approximately 2 mm and the restcontains the higher concentration of antioxidant.

One puck each (10 cm diameter, ˜6.4 mm thickness) is vacuum packaged andirradiated to 50, 75, 100, 150, 200, 250, 300, 350, 400 kGy by electronbeam irradiation (2.5 MeV generator, MIT) at 25 kGy/pass. Afterirradiation, the pucks are doped in antioxidant at 100, 120, 130, 150,180, 200, or 300° C. for 16, 40, 64, 88, 185 or 1000 hrs. After doping,they are homogenized in inert gas or supercritical carbon dioxide at100, 120, 130, 150, 180, 200, or 300° C. for 16, 40, 64, 88, 185 or 1000hrs.

Example 34. Warm Irradiation of Irganox® Blends

GUR1050 UHMWPE pucks are prepared as described in FIG. 42a by layeredcompression molding of 1 wt % vitamin E-blended UHMWPE in one layer and0.05 wt % Irganox® 1010-blended UHMWPE resin powder in the other layer.Blending of the antioxidants into the powder is made by dissolving inIPA, mixing the solution with UHMWPE powder, and evaporating the solventby vacuum drying at 60° C. The thickness of the layer molded with lowIrganox® concentration is approximately 2 mm and the rest contains thehigher concentration of vitamin E.

The layered compression molded puck is pre-heated to an elevatedtemperature below the melting point of UHMWPE, for example 25, 50, 70,100, 120, 125, or 135° C. Then the pre-heated material is irradiated to25, 50, 100, 150, and 200 kGy by electron-beam or gamma irradiation. Thee-beam irradiation is carried out in either one pass for the totaldesired dose or in multiple passes. In some embodiments the dose appliedin each pass is ¼, ½, ⅓, ⅕, ⅙, or 1/7^(th) of the total desired dose.The pucks are either packaged in inert gas or irradiated in air.

Control samples are prepared by compression molding pucks with uniformconcentrations of vitamin E and Irganox® using 1 wt % vitamin E-blendedUHMWPE and 0.05 wt % Irganox®-blended UHMWPE. These controls areirradiated with and without pre-heating to the same temperatures aslisted above.

Example 35. Decomposition of UHMWPE as a Function of Temperature

In order to assess the thermal stability of UHMWPE at high temperatures,TGA was performed by using a Q-500 Thermogravimetric analyzer (TAInstruments Inc., Newark, Del.). One sample (about 10 mg) was loaded onthe pan and heated up to a target temperature (280, 300, 320, 340, and400° C.) at 20° C./min and held at the temperature for 1440 min undernitrogen flow at 60 ml/min. The weight over time was sampled every 30seconds. The remaining weight percentage was plotted against time tocompare the thermal stability of UHMWPE at different temperatures.

There was no significant decomposition of UHMWPE within 24 hours when itwas heated to below 340° C. (FIG. 60).

Example 36. High Temperature Melting of GUR1050 UHMWPE in an Inert GasConvection Oven

Compression molded GUR 1050 UHMWPE (CM UHMWPE) (Orthoplastics, BacupLancashire, UK) with dimensions of 250×60×45 mm³ (length×width×height)were melted in a programmable inert gas convection oven (DespatchIndustries, Minneapolis, Minn.) under continuous nitrogen flow (flowrate was ˜2 m³/min). The oven was preheated to a preset temperature withnitrogen purge. Then, the UHMWPE blocks were placed in the oven andpurged again. Three temperatures (280, 300, and 320° C.) were used tomelt the UHMWPE. At each temperature, the UHMWPE was held for 2, 5, or12 h and then cooled down to 40° C. within 2 h (or an average coolingrate of 2.5° C./min or less). The samples were held at 40° C. for 20 minin the oven before retrieval. Such melted UHMWPE was denoted as HTMUHMWPE. Specifically, the HTM UHMWPE samples were denoted as UH T-t,where T is the melting temperature and t is the melting duration; forexample UH 280-2, UPI 280-5, and UH 280-12 represent UHMWPE melted at280° C. for 2, 5, and 12 h, respectively.

Thin sections (thickness=3.2 mm) were machined (Eastern Tool Inc,Medford, Mass.) from HTM UHMWPE and CM UHMWPE. Tensile testing specimens(Type V, n=5) were stamped from these thin sections according to ASTMD638. Uni-axial tensile testing was conducted by using an MTS machine(Eden Prairie, Minn.) at a crosshead speed of 10 mm/min. The axialdisplacement and force were sampled at a rate of 100 Hz. The extensionof a specific gauge on the specimen was measured by a laserextensometer, which was used to determine the elongation at break (EAB).

True stress-true strain curves were converted from the engineeringstress-strain results by using the extension readings from the laserextensometer. The ultimate tensile strength (UTS); yield strength (YS),work to failure (area under the engineering stress-strain curve; WF),and elastic modulus (E) were calculated. Statistical analysis wasperformed by using a Student's t-test for two-tailed distributions withunequal variance where applicable.

The strain-hardening modulus (G) is regarded as the intrinsic propertyof an entangled amorphous network. According to the Gaussian model byHaward and Thackray, (Haward R N. Macromolecules 1993; 26:5860-5869) thetrue stress (σ) and G are related byσ=G(λ²−1/λ)+Y  (1)

where λ is the extension ratio and λ=exp(ε_(t)) with ε_(t) as truestrain, and Y is the flow stress exerted by the crystalline phaseincluding intra- and interlamellar coupling. In order to calculate thestrain-hardening modulus of the amorphous phase in this semi-crystallinepolymer, we deduced the Haward plots from the true stress-strain curvesand extracted the slope of the fitted line after yielding.

Double-notched Izod impact strength measurements were conducted atOrthoplastics Inc. (Bacup Lancashire, UK). The specimens (n=5 for eachmaterial) were machined to 63.5×12.7×6.35 mm³ bars and double notched toa depth of 4.57±0.08 mm according to ASTM F648. The specimens wereconditioned after notching for not less than 16 h at 23±2° C. and testedin accordance with ASTM F648. The energy absorbed by the specimens wasrecorded for the calculation of the impact strength in kJ/m².

In order to evaluate the chain scission in UHMWPE by high temperaturemelting, the melted samples were microtomed into thin slices(thickness=150 μm) by using an LKB Sledge Microtome (Sweden). FTIRabsorption spectra of these thin slices were collected by using aUMA-500 infrared microscope (Bio-Rad Laboratories, Natick, Mass.)scanning from 400 to 4000 cm⁻¹ (step width 2 cm⁻¹) in transmission mode.Chain scissioning taking place in UHMWPE at high temperatures led to theformation of terminal vinyl groups with absorbance at 909 and 990 cm⁻¹.The content of these terminal vinyl groups was indexed by normalizingthe integral of the peak at 909 cm⁻¹ against that of the polyethyleneskeleton peak at 1895 cm⁻¹. These vinyl indices were taken as anindication to the extent of chain scission occurring in UHMWPE underhigh temperatures.

The bi-directional POD wear test was performed on an MTS machine (EdenPrairie, Minn.) in bovine serum. Pins of 13-mm length and 9-mm diameter(n=3 for each material) were machined and mounted on the MTS wear testerto undergo bi-directional motions on polished CoCr discs at 2 Hz and astep length of 5×10 mm under a maximum load of 1.9 kN. The pins wereweighed at every 157 kilo-cycle until a total of 1 million cycles (MC)and the weight loss from 0.5 to 1 MC were used to evaluate thegravimetric wear rate in milligram per million cycles (mg/MC).

Increasing temperature and increasing duration during high temperaturemelting increased the vinyl index, suggesting increased chainscissioning (FIG. 61a ). Increasing chain scissioning was directlycorrelated to increasing elongation-at-break (FIG. 61b ) and anon-linear decrease in the strain-hardening modulus (FIG. 61c ).

The ultimate tensile strength (UTS) was not significantly changed untilthe vinyl index reached approximately 0.06, after which there was asignificant decrease in the UTS (FIG. 62a ). Similarly, the tensilework-to-failure (WF) increased until the vinyl index reachedapproximately 0.06, after which there was a significant decrease in theWF (FIG. 62b ). There was a slight increase in the IZOD impact strengthas a function of vinyl index at a vinyl index of 0.02-0.04, after whichthere was a decrease, significantly after a vinyl index of 0.06 (FIG.62c ). Nevertheless, there was not a significant increase in the wearrate of UHMWPE as a function of increasing elongation-at-break (EAB)until an EAB of over 1000% (FIG. 62d ).

The mechanical properties, wear rates and significance values are shownin Table 21. We attribute the elimination of structural defects throughthe self-diffusion of the UHMWPE chains for the increase in the tensiletoughness (WF) and the impact strength. At conventional moldingtemperatures (T_(p)<200° C.), self-diffusion is very slow and the timerequired for the UHMWPE chains to reptate (De Gennes P-G. Scalingconcepts in polymer physics, 4 ed. Ithaca: Cornell University Press,1979) through the highly viscous UHMWPE melt (>15 h) (Rastogi S, LippitsD R, Peters G W M, Graf R, Yao Y, and Spiess H W. Nature Materials 2005;4: 635) is much longer than the typical molding time (≦0.5 h). Inparticular, it is more difficult for the chains to reptate across thegranule boundaries, where there are no entanglements before molding.This explains the presence of the granule with explicit boundaries (FIG.39a ) on the freeze-fractured surface of the as-molded CM UHMWPE. Theseboundaries could serve as structural defects with low toughness that maylead to the initiation of cracks under cyclic loading. At hightemperatures, the melt viscosity is reduced and the chain mobility isenhanced, whereas some UHMWPE chains were cleaved. As a result,self-diffusion via chain reptation through the tube defined by theneighboring chains (Doi M and Edwards S F. The Theory of PolymerDynamics. Oxford: Clarendon, 1986) is accelerated, Thus, the granulesfurther fused and the chain entanglements were improved, leading to theformation of spherulites without distinct boundaries afterrecrystallization (FIG. 39b ). The structural defects were eliminatedand the stress concentration could be largely reduced.

Example 37. Mechanical and Wear Properties of High Temperature Meltedand Irradiated UHMWPEs

Compression molded GUR 1050 UHMWPE (CM UHMWPE) (Orthoplastics, BacupLancashire, UK) with approximate dimensions of 250×60×45 mm³(length×width×height) were melted by using a programmable convectionoven with inert gas capability (LLD1-16N-3, Despatch Industries,Minneapolis, Minn.). The oven was preheated to a preset temperature withnitrogen purge (flow rate ˜2 m³/min). Then, the UHMWPE was placed in theoven and was held at temperature for different durations. Thetemperatures used were 280, 300, and 320° C. At each temperature, theUHMWPE was held for 2, 5, or 12 h and then cooled down to 40° C. within2 h (at an average cooling rate of 2.5° C./min) and held at 40° C. for20 min in the oven before retrieval. These melted UHMWPEs were denotedas UH T-t, where T is temperature, and t is time. For example, UH 280-2denotes a UHMWPE stock melted at 280° C. for 2 h.

The HTM UHMWPEs (HTM-PE) were vacuum packed and cross-linked by using a10 MeV electron beam at room temperature at Iotron Inc. (Vancouver, BC)at a dose rate of 50 kGy/pass. The total doses were 50, 100, and 150kGy, CM UHMWPE blocks without HTM treatment were irradiated as controls.The control samples were denoted as XL-PE-50, XL-PE-100, and XL-PE-150and the irradiated HTM-PEs were denoted as UHI T-t-D, where T istemperature, t is time, and D is radiation dose. For example, UHI280-2-50 denotes a UHMWPE melted at 280° C. for 2 h and then e beamcross-linked with a dose of 50 kGy.

The mechanical testing and wear testing and vinyl index calculationswere done as described in the previous example. Crosslink densitymeasurements of cross-linked UHMWPE (n=3 each) were performed on smallsamples (approximately 3×3×3 mm). The samples were weighed beforeswelling in xylene at 130° C. and they were weighed immediately afterswelling in xylene. Therefore, the amount of xylene uptake wasdetermined gravimetrically, then converted to volumetric uptake bydividing by the density of xylene; 0.75 g/cc. By assuming the density ofpolyethylene to be approximately 0.99 g/cc, the volumetric swell ratioof crosslinked UHMWPE was then determined. The cross-link density wascalculated using the swell ratio as described previously (Muratoglu atal. Biomaterials 20:1463-1470 (1999)) and is reported as mol/m³.

At the same crosslink density, high temperature melted, then radiationcrosslinked UHMWPEs had lower wear rates than irradiated, then meltedUHMWPEs without high temperature treatment (FIG. 63).

The elongation-at-break (EAB) of both irradiated high temperature melted(HTM) UHMWPEs and irradiated UHMWPEs without HTM showed the samelogarithmic dependence on cross-link density (FIG. 64a ). However,irradiated HTM UHMWPEs had lower crosslink density than non-HTM UHMWPE,thus their EAB was higher. Similarly, IZOD impact strength showed a weaklinear decrease with increasing crosslink density (FIG. 64b ), but theimpact strength values for irradiated HTMs were much higher at the sameradiation dose due to lower crosslink density (Table 22). The ultimatetensile strength (UTS) of irradiated HTM UHMWPEs were unaffected bychanges in crosslink density whereas irradiated UHMWPEs without HTMtreatment showed a large decrease with increasing crosslink density(FIG. 64c ).

FIGS. 64a-c illustrates the effect of crosslink density on theelongation-at-break (64 a), IZOD impact strength (64 b) and ultimatetensile strength (64 c) of radiation crosslinked UHMWPEs. Samples wereirradiated and melted UHMWPE without high temperature melting (CISM).These samples have been melted at approximately 170° C. afterirradiation for less than 5 hours. The open symbols are irradiatedUHMWPEs with prior high temperature melting.

The lower crosslink density of irradiated HTM UHMWPEs was correlated tothe amount of chain scissioning due to HTM prior to irradiation. Thehigher the pre-irradiation vinyl index (thus increased chainscissioning), the lower was the crosslink density (FIG. 65). FIG. 65illustrates the effect of the initial vinyl index before irradiation onthe crosslink density of irradiated high temperature melted UHMWPEs. Thesamples were irradiated and melted UHMWPE without high temperaturemelting (CISM). These samples also have been melted at approximately170° C. after irradiation for less than 5 hours.

The physical, mechanical and wear properties of irradiated, hightemperature melted UHMWPEs are shown in Table 22.

Example 38. Oxidative Stability of Irradiated, HTM UHMWPE by AntioxidantIncorporation

Blends of vitamin E with GUR1050 UHMWPE were prepared by makingsolutions of vitamin E in isopropyl alcohol (IPA), mixing the solutionwith UHMWPE powder and vacuum drying the powder at 60° C. until thesolvent was evaporated. In this manner, concentrated (2 wt %) blendswere made and diluted with UHMWPE powder if desired. Blends of UHMWPEcontaining 0.1 and 0.2 wt % vitamin E were compression molded intocylindrical pucks (diameter 10 cm, thickness ˜1 cm) using an automaticlaboratory press. One puck each was melted at 280, 300 or 320° C. for 2,5 or 12 hours as described in the previous example. Then the HTM puckswere packaged in vacuum and irradiated to 50, 100 and 150 kGy usingelectron-beam irradiation. Samples were machined into 1 cm cubes.

Two accelerated aging methods were used: 14 days at 70° C. under 5 atm.of oxygen (ASTM F2003) and 14 days at 70° C. under 5 atm. of oxygenafter squalene doping. Squalene is an unsaturated lipid, which initiatedsevere oxidation in irradiated and melted UHMWPE. Cubes (1 cm) weremachined from Irganox® 1010 blended pucks and irradiated blended pucks.Squalene doping was done in pre-heated squalene at 120° C. for 2 hours.

After accelerated aging, the 150 μm-thick sections were microtomed froman inner surface (FIG. 43; n=3 each). These sections were boiled inhexane overnight and then dried in vacuum at room temperature for 24hours. They were then analyzed by FTIR. An oxidation index wascalculated as a function of depth away from the surface as the ratio ofthe areas under 1680 cm⁻¹-1780 cm⁻¹ to the absorbance over 1370 cm⁻¹ perASTM F2003.

Both high temperature inciting before irradiation and vitamin E-blendingprior to high temperature melting and irradiation increased theoxidative resistance of UHMWPE under accelerated aging without squalene(FIG. 66a ) and in the presence of squalene (FIG. 66b ). FIGS. 66a-bshow post-hexane oxidation of accelerated aged 150-kGy irradiated virginUHMWPE and 0.2 wt % vitamin E-blended UHMWPE with and without hightemperature melting at 300 and 320° C. for 5 hours. Accelerated agingwas performed at 70° C. for 14 days at 5 atm. of oxygen (66 a).Accelerated aging was performed at 70° C. for 14 days at 5 atm. ofoxygen after squalene doping at 120° C. for 2 hours (66 b).

Example 39. Various Methods and Options for Making Surface CrosslinkedJoint Implants

Various methods of making surface crosslinked joint implants accordingto the invention are described in more details in the followingillustrative examples. Although these examples may represent onlyselected embodiments of the invention, it should be understood that thefollowing examples are illustrative and not limiting.

FIGS. 67a-f illustrate schematic of a generic tibial insert with regionscontaining different concentrations of antioxidant. For example, theshaded regions contain Irganox® 1010 at a low concentration such as 0.05wt % and the other regions contain higher concentration of antioxidantsuch as 1 wt % vitamin E, FIGS. 67a-f depict the top (articular surface)view of a generic tibial insert—the tibial insert could be symmetric onthe medial and lateral sides or anti-symmetric.

FIG. 68 depicts the top (articular surface) view of a generic acetabularliner. The shaded regions depict examples of implant surfaces whichcontain a different concentration of antioxidant than the not shadedregions. The intended purpose of having low concentration of antioxidantin the shaded regions is to obtain high levels of crosslinking in theseregions after exposure to irradiation (FIG. 69). These types of surfacescan be obtained by layered molding of polymer blends with differentantioxidants and different antioxidant concentrations. In the unshadedregions, an anti-crosslinking agent is used. This can be an antioxidantsuch as vitamin E or a mixture of antioxidants such as Irganox® 1010 andvitamin E. The concentrations are determined depending on the level ofcrosslinking desired in the shaded and unshaded regions. For example, 1wt % vitamin E in the unshaded regions and 0.05 wt % Irganox® 1010 inthe shaded regions can be used. Subsequently, the tibial inserts withdifferent layers of polymer blends, examples as shown in FIGS. 67b-f ,can be irradiated to 25, 50, 75, 100, 125, 150, 175, 200, 250 or 300kGy.

Such shapes can be obtained by direct compression molding of layers ofpolymer blends with antioxidants/anti-crosslinking agents.Alternatively, these compression molded shapes can be further machinedfrom the articular or backside surfaces or in other parts of the implantfor example to machine locking mechanisms.

Another method by which these surfaces can be obtained is bypreferentially extracting the antioxidants/anti-crosslinking agents thatwere blended into the polymer resin and compression molded after moldingbefore exposure to irradiation.

Alternatively, these implants can be machined from a previouslyconsolidated (ram extrusion, compression molding, direct compressionmolding) UHMWPE/antioxidant blend. The implants are then subjected to anextraction procedure to remove surface antioxidant. The removal from theimplants can be preferential by masking areas where extraction is notdesired.

FIGS. 68 a-e show schematic of a generic acetabular liner(crosssectional view) with surface regions containing a lowconcentration of antioxidant, where the surface region containing a lowamount of antioxidant can cover entirely or partially top surface of theimplant (68 a). Low concentration of antioxidant can be contained onboth the top and backside surfaces of the implant (68 b). In addition,low concentration of antioxidant can be contained on the top and/orbackside surfaces of the implant such that locking mechanisms can bemachined into regions with high concentration of antioxidant (68 c, 68d), Examples of surface regions (top view) with varying antioxidantconcentration are shown in FIG. 68e . For example, the shaded regionscontain Irganox® 1010 at a low concentration such as 0.05 wt % and theother regions contain higher concentration of antioxidant such as 1 wt %vitamin E.

Extraction of the antioxidants from the surfaces of the implant can beused either on a molded polymer or molded implant with a uniformconcentration of antioxidant/anti-crosslinking agent or on a moldedpolymer or molded implant that already has a gradient ofantioxidant/anti-crosslinking agent. In this manner, the concentrationof at least one antioxidant/anti-crosslinking agent is lowered in thesurface regions. Subsequent exposure to irradiation results in adifferent crosslink density in these surface regions than if they arenot extracted before irradiation. Extraction can be applied uniformly tothe surfaces such as in FIG. 68c or it can be applied preferentiallysuch as in FIG. 68e by masking parts of the surface.

FIG. 69 shows schematic of a hip implant with a highly crosslinkedarticular surface made by direct compression molding of layers of apolymer blend with a high concentration of vitamin E and a polymer blendwith a low concentration of an antioxidant from the Irganox® family suchas Irganox® 1010.

Example 40. Wear Rate as a Function of Depth of Surface CrosslinkedUHMWPE Prepared by Extraction

Blends of vitamin E with GUR1050 UHMWPE were prepared by makingsolutions of vitamin E in isopropyl alcohol (IPA), mixing the solutionwith UHMWPE powder and vacuum drying the powder at 60° C. until thesolvent was evaporated. In this manner, concentrated (2 wt %) blendswere made and diluted with UHMWPE powder if desired. Blends of UHMWPEcontaining 0.5, 1, 1.5 and 2 wt % vitamin E were compression molded intocylindrical pucks (diameter 10 cm, thickness ˜1 cm) using an automaticlaboratory press. These pucks were then machined into cylindrical pins(9 mm diameter, 13 mm length) for wear testing.

These pins were boiled in a 20 v/v % aqueous solution of Tween 20 underreflux for 40 hours to extract the vitamin E from the surface regions.Then the extracted pins were irradiated by e-beam irradiation to 150kGy. To determine the spatial variation of the antioxidant concentrationthroughout the samples, 150 μm-thick sections were microtomed from aninner surface (FIG. 43; n=3 each) were analyzed using FTIR. Vitamin Eindex was calculated as the ratio of the areas under 1245 cm⁻¹-1275 cm⁻¹to the absorbance over 1875 cm⁻¹-1905 cm⁻¹. The vitamin E concentrationprofiles for 0.5 wt % vitamin E blended and extracted UHMWPE before andafter 150 kGy irradiation are shown in FIG. 70 a.

Wear rates were determined by pin-on-disc wear testing on acustom-designed bidirectional wear tester (see Bragdon C R, O'Connor DO, Lowenstein J D, Jasty M, Biggs S A, Harris W H. A new pin-on-discwear testing method for simulating wear of polyethylene on cobalt-chromealloy in total hip arthroplasty. Journal of Arthroplasty 2001: 41(2):795-808). Testing was performed in undiluted preserved bovine serum at 2Hz for approximately 1.2 million cycles (MC) with gravimetric assessmentof wear at approximately every 250,000 cycles. Wear rate was determinedas a linear regression of weight loss as a function of number of cyclesfrom 0.5 to 1.2 MC.

Wear rates were determined as a function of depth by machining awayapproximately 150 μm from the surface after each wear test was completedand re-testing the samples. The wear rates as a function of depth awayfrom the surface are shown for 0.5 wt % vitamin E-blended, extracted and150 kGy irradiated UHMWPE in FIG. 70b . The wear rates a function ofdepth away from the surface are shown for 1.0 wt % vitamin E-blended,extracted and 150, 200, 250 or 300 kGy irradiated UHMWPE in FIG. 70 c.

It is to be understood that the description, specific examples and data,while indicating exemplary embodiments, are given by way of illustrationand are not intended to limit the present invention. Various changes andmodifications within the present invention will become apparent to theskilled artisan from the discussion, disclosure and data containedherein, and thus are considered part of the invention.

What is claimed is:
 1. A method of making a wear resistant polymericmaterial comprising the steps of: (i) blending a polymeric material withat least one type of antioxidant and one type of peroxide to form ablended polymeric material; (ii) consolidating the blended polymericmaterial; (iii) heating the consolidated blended polymeric material at atemperature that is about 200° C. or more at about ambient pressure;(iv) continue heating the consolidated polymeric material; and (v)cooling the heated material to below the melting temperature of thepolymeric material, thereby forming a wear resistant polymeric material.2. The method according to claim 1, wherein the wear resistant polymericmaterial is machined into a medical implant.
 3. A method according toclaim 2, wherein the medical implant is further packaged and sterilized.4. A method according to claim 3, wherein the sterilization is done bygamma irradiation.
 5. The method according to claim 1, wherein thepolymeric material is machined after the consolidating.
 6. The methodaccording to claim 1, wherein the heating of the consolidated polymericmaterial is above 200° C. and is continued for at least 2 hours.
 7. Amedical implant comprising a wear resistant polymeric material madeaccording to claim 1, wherein the wear resistant polymeric material ismachined into the medical implant.
 8. The medical implant of claim 7 isfurther packaged and sterilized.
 9. The medical implant of claim 8,wherein the sterilization is done by gamma irradiation.
 10. The methodaccording to claim 1, wherein the heating is performed in an inertatmosphere.
 11. The method according to claim 1, wherein the heating iscarried in air or in an atmosphere containing oxygen, wherein the oxygenconcentration is at least about 1%, 2%, 4%, or up to about 22%.
 12. Themethod according to claim 1, wherein the antioxidant is a phenolicantioxidant, vitamin E, or a mixture thereof.
 13. The method accordingto claim 12, wherein the phenolic antioxidant is PentaerythritolTetrakis (3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate).
 14. Themethod according to claim 1, wherein the polymeric material iscompression molded as a single layer containing one or moreantioxidants.
 15. The method according to claim 1, wherein the polymericmaterial is compression molded as multiple layers, wherein the layerscontain different concentrations of one or more antioxidants.
 16. Themethod according to claim 1, wherein the polymeric material iscompression molded to a second surface, thereby forming an interlockedhybrid material.
 17. The method according to claim 1, wherein thepolymeric material is selected from the group consisting of alow-density polyethylene, high-density polyethylene, linear low-densitypolyethylene, ultra-high molecular weight polyethylene (UHMWPE), or amixtures thereof.
 18. The method according to claim 1, wherein thepolymeric material is ultra-high molecular weight polyethylene (UHMWPE).